Immunological investigations (IMMUNOL INVEST)

Publications in this journal

• Article: Current trends and investigative developments in celiac disease.

  Gabriel Samaşca, Genel Sur, Iulia Lupan
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  ABSTRACT: Celiac disease has become extensively studied. What could be the cause? Increasing the accuracy of diagnostic tests for celiac disease has led to more discovered cases. Serological diagnosis of celiac disease has undergone important changes in recent years. Application of serological tests has reflected the diagnostic performance of tissue transglutaminase antibody and endomysial antibody as screening tests for celiac disease but also the progress of new serological tests as the antibodies against synthetic deamidated gliadin peptides. Serological tests are largely responsible for the recognition that celiac disease is not a rare disease. The Consensus in celiac disease from 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition which agreed that “Celiac disease is an immune-mediated enteropathy that can affect any system or organ and that can present itself with a wide range of clinical manifestations of variable severity” was confirmed. But increasing prevalence of this disease has led to the need for new methods of treatment among patients with celiac disease. Studies on quality of life of patients with celiac disease have questioned the gluten-free diet. As such new therapies, like TG2 inhibitors, the copolymer P (HEMA-co-SS) and other new experimental therapies, have emerged in celiac disease. The new therapies in celiac disease are based on new investigations in gluten toxicity screening, like K562(S)-cell agglutination, A1 and G12 monoclonal antibodies and proteomics. In this paper we want to present the investigative developments in celiac disease. We also want to find whether a new treatment in celiac disease is necessary.
  Immunological investigations 05/2013; 42(4):273-284.
• Article: The immunopathology of the small intestinal reaction in gluten-sensitivity.

  M N Marsh
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  ABSTRACT: Computerised image-analysis was used to define the spectrum of immunopathological changes in small intestinal mucosa in established celiac sprue disease; dermatitis herpetiformis; 1 degree relatives of celiac sprue patients, and treated celiac sprue patients challenged with varying doses of a peptic-tryptic digest of gluten. Typically, in flat ('Type 2') lesion there was a reduced number of large, mitotically active lymphocytes in surface epithelium, but an increased lymphocyte population in crypts. In approximately 50% untreated DH patients and in 20% 1 degree celiac sprue relatives, mucosal architecture was well-preserved although surface (villous) epithelium contained an expanded population of small, non-mitotic lymphocytes ('Type 1' lesion), with or without crypt hyperplasia. Similar changes were also induced by small dose gluten challenge. Larger dose challenges caused a progression from a Type 1 to a Type 2 lesion during a 5 day period of observation. In addition, observations on a few patients over 2-4 years showed a similar sequence of mucosal changes. A major feature of this sequence was the early appearance of crypt hypertrophy, before significant villous flattening had occurred. These changes parallel T lymphocyte-mediated graft- versus-host reactions in animals, suggesting that the specific immunopathologic features seen in gluten sensitivity are fundamentally cell-mediated in type, the degree of change probably dependent on host genetic factors. Finally, these data show that in becoming flat the mucosa must initially pass through the earlier Type 1 lesion in which crypt hypertrophy is a prominent response.
  Immunological investigations 07/2009; 18(1-4):509-31.
• Article: Polymerase chain reaction assays for the detection of cytomegalovirus in organ and bone marrow transplant recipients.

  M J Evans, Y Edwards-Spring, J Myers, A Wendt, D Povinelli, D Amsterdam, K Rittenhouse-Diakun, D Armstrong, B M Murray, S J Greenberg, M Riepenhoff-Talty
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  ABSTRACT: Cytomegalovirus (CMV) infection is ubiquitous and results in a wide spectrum of clinical manifestations ranging from asymptomatic infection to severe life threatening disease. Infection in normal children and adults usually causes no symptoms but in the immunocompromised host, CMV may result in severe opportunistic infections with high morbidity and mortality. Historically, virus detection was dependent on culture of the virus or on a centrifugation culture system referred to as a shell vial assay. The shell vial assay frequently lacked sensitivity and was unable to detect infection in its early phase. Also, as with culture assays, the results were affected by antiviral therapy. The CMV antigenemia assay was developed to provide more rapid results and has gained wide usage. This assay is limited to detection of the virus in white blood cells and is more sensitive than culture or the shell vial assay. Application of the polymerase chain reaction (PCR) to these problems has resulted in the development of assays for CMV which are more sensitive than previously available methods. This method employs liquid hybridization with 32P labeled probes and gel retardation analysis for detection of amplified DNA specific for each virus. A comparison of the detection of CMV by an antigenemia assay or the PCR method in the leukocytes of renal transplant patients revealed that the PCR assay detects cytomegalovirus earlier and more consistently than the antigenemia assay. Finally, the application of a fluorescent dye detection system and image analysis of the acrylamide gel with a laser scanner provides additional sensitivity to the detection of cytomegalovirus, as well as avoiding the use of radioactivity, making the assay more adaptable to the clinical laboratory.
  Immunological investigations 07/2009; 26(1-2):209-29.
• Article: Differential transcriptional control of the H-2K and H-2D loci of the major histocompatibility complex in fibrosarcoma cells.

  M Aboud, H Amitai, M Huleihel, I Har-vardi, J Gopas, S Segal
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  ABSTRACT: In this study we demonstrate a differential transcription of H-2K and H-2D class-I genes in two different tumor cell clones; one is highly metastatic (IE-7) and the other is not metastatic (IC-9), both derived from the same fibrosarcoma, T-10, induced in an (H-2b x H-2k)F1 mouse. The expression of the two parental H-2K alleles is transcriptionally suppressed in both of these clones. In addition the IC-9 clone does not transcribe also the H-2Dk allele. Our data rule out the possibility that this suppression results from enhanced RNA degradation, impaired polyadenylation, DNA rearrangement, or changes in DNA methylation within these genes. Interferons (IFN) are known to enhance MHC expression by acting on a consensus IFN responsive element present in the promoter region of MHC genes. However, IFN-gamma, which is the most potent IFN in this respect, failed to activate the expression of the silent MHC genes in our cells. This finding may reflect a defect within the promoter region of these genes or changes in their chromatin structure.
  Immunological investigations 07/2009; 20(5-6):475-85.
• Article: Murine Bone Marrow-Derived Mast Cells Exhibit Evidence of Both Apoptosis and Oncosis After IL-3 Deprivation

  Bong Soo Park, Gyoo Cheon Kim, Soo Jin Baek, Nam Deuk Kim, Yang Soon Kim, Seok Kwon Kim, Min Ho Jeong, Young Jin Lim, Young Hyun Yoo
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  ABSTRACT: IL-3 deprivation has been reported to induce apoptosis of bone marrow-derived mast cells. In order to evaluate this type of cell death further, we employed trypan blue and propidium iodide stainings, photometric enzyme immunoassay, fluorescence measurement of caspase-3, DNA electrophoresis, flow cytometry and transmission electron microscopy. In this experiment, although several evidences supporting apoptosis were demonstrated some findings were not consistent with typical apoptosis. On the other hand, electron microscopical observation demonstrated that most cells from all the time phases after IL-3 deprivation showed the morphology of typical oncosis, i.e. cell swelling, disintegration of ultrastructure and subsequent karyolysis. Only a small number of cells from the later time phases showed apoptotic morphology. We here suggest that BMMCs undergo both apoptosis and oncosis after IL-3 deprivation and that the dominant type of prelethal change is oncosis in all time phases, although apoptosis also plays a partial role in the late time phases.
  Immunological investigations 07/2009; 29(4):51-60.
• Article: Production and characterization of an anti-idiotypic single chain Fv that recognizes an anti-DNA antibody.

  Myung-Hee Kwon, Myung-Shin Lee, Kyongmin Hwang Kim, Sun Park, Ho-Joon Shin, Young-Ju Jang, Hyung-Ii Kim
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  ABSTRACT: A well-characterized recombinant anti-idiotype to an anti-DNA antibody can be useful for studies of the regulation of anti-DNA-producing B cells. Using a hybridoma technique, a monoclonal anti-idiotypic antibody, designated O2F3, was obtained, and its scFv gene was constructed. O2F3 single chain Fv (scFv) was produced against an idiotope of a monoclonal anti-DNA antibody, 3D8, that was obtained from an autoimmune-prone mouse, MRL-lpr/lpr. Here we describe the production and in vitro characterization of the O2F3 scFv, and compare it with its parent monoclonal antibody, O2F3 IgM. To characterize O2F3 scFv and O2F3 IgM, we generated recombinant 3D8 fragments, including 3D8 scFv, 3D8 VH, and 3D8 VL, that were used as antigens in several assays. ELISA and Western blot analysis showed that both O2F3 scFv and O2F3 IgM recognized a conformational determinant formed by the association of the variable region heavy and light chains of the 3D8 antibody, suggesting that O2F3 scFv retained a similar binding pattern to its parent O2F3 antibody. The idiotope recognized by O2F3 was shown by competitive ELISA to be outside of the DNA binding site of the 3D8 antibody. This characterized O2F3 scFv could be applied for the regulation of anti-DNA antibody production and the manipulation of recombinant antibody-based proteins to which toxins, enzymes, and chemical agents can be connected.
  Immunological investigations 07/2009; 31(3-4):205-18.
• Article: Thermodynamics of Monoclonal and Mixed Cryoimmunoglobin Solubilization

  Duane T. Brandau, Erlinda Q. Lawson, Philip A. Trautman, C. Russell Middaugh
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  ABSTRACT: The direct calorimetric determination of heats of solution for four monoclonal and three mixed (IgM/IgG) cryoglobulins is described. Values obtained by differential scanning calorimetry (DSC) are compared to values of the apparent δHsol obtained by a polyethylene glycol (PEG) precipitation method. The four monoclonal cryoglobulins manifest heats of solution determined by DSC to be of the same order of magnitude as heats obtained by PEG precipitation, although DSC values were 25 to 125% lower than the corresponding van't Hoff enthalpies. Values of δH sol for mixed cryoglobulins were significantly greater than monoclonal cryoglobulins on a molar basis. These higher values are primarily attributed to the greater surface area of these complexes which results in more extensive contact between molecules in the solid phase. No evidence was found that conformational changes contributed to the calorimetric δHsol values employing a variety of spectroscopic methods.
  Immunological investigations 07/2009; 16(1):21-32.
• Article: The Deposition of C5b-9 Complexes and Its Precursors on E. coli J5 During Complement Activation Enhances Uptake and Toxicities of Gentamicin

  Earl Bloch, Kasey Morrison, Shelly McDonald-Pinkett, Sheena Baskin, Stephanie Campbell, Sharla Peters, Sandra Dillahunt, Dia Evans, Shantelle Lucas, Aimee Macatangay, Yasmine Kanaan
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  ABSTRACT: The complement system provides the host with protection against pathogenic agents and in some cases can result in damage to host tissue. However, the exact mechanism of how complement kills Gram-negative bacteria in lysozyme-neutralized and or lysozyme-depleted serum is still under active investigation. In previous studies, it has been demonstrated that inner membrane damage by the membrane attack complex contributes to depolarization and the subsequent collapse of the membrane potential. In these studies we have shown that the membrane attack complex and its precursors provide additional protective effect by the enhanced uptake of antibiotics in the death of E. coli J5. Specifically, the deposition of C5b fragments from C6 neutralized Pooled Normal Human Serum (PNHS) and C5b6 complexes from C7 neutralized PNHS on E. coli J5 contribute to antibiotic uptake and killing. Since C5b and C5b6 do not form pores, we suggest that disturbances and or cracks in the outer membrane by the deposited complexes accelerates uptake of the antibiotics and enhanced killing of E. coli J5 employed in these studies.
  Immunological investigations 03/2008; 37(3):245-261.
• Article: Neutrophils induce the maturation of immature dendritic cells: a regulatory role of neutrophils in adaptive immune responses.

  Wan Xiaoxiao, Yue Sibiao, Xiong Xiaopeng, Zheng Ping, Chen Gang
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  ABSTRACT: Th1-type immune cytokines are essential to establish adaptive immunity against various microbial pathogens, including Escherichia coli, which cause most urinary tract infections (UTIs). Dendritic cells (DCs) are vital to initiate Th1 immunity, while neutrophils, also referred to here as polymorphonuclear leukocytes (PMN) are reported to be involved in Th1 immunity initiation by secreting several chemokines and cytokines. We found that lipopolysaccharide (LPS)-triggered PMN (LPS-PMN) in vitro induced strong up-regulation of DCs surface markers CD40, CD80, MHC-II (Iab), and CD86 either by secreting soluble factors, such as TNF-alpha, or by PMN-DC cellular contact. LPS-PMN also stimulated DCs to produce IL-12 and TNF-alpha. Furthermore, purified DCs activated by LPS-PMN were able to present specific antigen to T cells and drive Th1 differentiation by producing large amount of IFN-gamma but low amount of IL-4. Our results suggest a regulatory role of PMN for DCs function in adaptive immune responses, thereby providing a link between innate and adaptive immunity.
  Immunological investigations 02/2007; 36(3):337-50.
• Article: Anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells.

  Thongchai Taechowisan, Pittaya Tuntiwachwuttikul, Chunhua Lu, Yuemao Shen, Saisamorn Lumyong, Walter C Taylor
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  ABSTRACT: This research was undertaken to test the in vitro anti-inflammatory action of 5,7,4'-trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. The effects of the two coumarins were investigated on the formation of NO, PGE2, and TNF-alpha and also on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar effect was also observed when LPS-induced PGE2 release and COX-2 expression were tested. The inhibitory effects were shown in concentration-dependent manners. The 5,7,4'-Trimethoxy-4-phenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin also mildly but significantly reduced the formation of TNF-alpha.
  Immunological investigations 02/2007; 36(2):203-11.
• Article: Effect of AC II, an herbal formulation in cyclophosphamide-induced immunosuppression in BALB/c mice--Implication in HIV treatment.

  Sheeja T Tharakan, Girija Kuttan, Ramadasan Kuttan, M Kesavan, S Austin, K Rajagopalan
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  ABSTRACT: Effect of AC II, herbal drug formulation in reducing immunosuppression caused by administration of cyclophosphamide was studied. Mice were injected cyclophosphamide (CTX) 50 mg/kg b.wt. for 14 days with or without the drug and total WBC, bone marrow cellularity and alpha-esterase positive cells were determined. On day 15, total WBC count in cyclophosphamide treated mice was 1500 +/- 420 cells/mm3, while in AC II-treated mice it was 7658 +/- 376 cells/mm3. On day 16, administration of cyclophosphamide reduced bone marrow cellularity to 3.42 +/- 0.38 x 10(6) cells/femur from the normal value of 13.83 +/- 0.96 x 10(6) cells/femur. In AC II treated group bone marrow cellularity was increased to 8.05 +/- 0.7 x 10(6) cells/femur. The number of alpha-esterase positive cells was found to be reduced to 177 +/- 25 cells per 4000 cells in CTX treated groups. But in AC II-treated group the number of alpha-esterase positive cells were raised to 843 +/- 86 cells per 4000 cells, which was closer to that of normal (710 +/- 49 cells per 4000 cells). Results indicate the usefulness of AC II to combat immunosuppression induced by chemical and biological agents.
  Immunological investigations 02/2007; 36(2):147-57.
• Article: Combination of recombinant xenogeneic endoglin DNA and protein vaccination enhances anti-tumor effects.

  Guang-Hong Tan, Yue-Nan Li, Feng-Ying Huang, Hua Wang, Rui-Zhen Bai, Jie Jang
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  ABSTRACT: The immunization approaches with DNA vaccine priming and subsequent protein or peptide boosting has been widely tested in various models of infectious diseases. However, these approaches are seldom reported in the areas of cancer immunotherapy. In this study we combined endoglin plasmid DNA and recombinant protein as vaccines and used them to prime and boost, simultaneously, as a vaccine strategy. Our results showed that combination of endoglin DNA and protein vaccines could enhance both protective and therapeutic anti-tumor efficacy in both colon carcinoma and Lewis lung carcinoma models. Significant inhibition of tumor angiogenesis was found in the tumor tissues. The titers of autoantibodies against murine endoglin were significantly increased and the antibody levels lasted longer in the mice with combined endoglin DNA and recombinant protein vaccination. CTL response against endoglin-positive HUVECs, but not against endoglin-negative tumor cells was found in the mice combined DNA with protein vaccination. In addition, combination of endoglin DNA and recombinant protein vaccination significantly induced IFN-gamma secreting cells. These observations suggested that a combination of endoglin DNA and recombinant protein immunization as a vaccine strategy was superior to those using endoglin DNA or recombinant protein alone as vaccines.
  Immunological investigations 02/2007; 36(4):423-40.
• Article: Black grape and garlic extracts protect against cyclosporine a nephrotoxicity.

  Ilker Durak, Recep Cetin, Ozden Candir, Erdinç Devrim, Bülent Kiliçoğlu, Aslihan Avci
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  ABSTRACT: The aim of this study was to determine if the natural antioxidant foods, dried black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two Sprague-Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the antioxidant food supplementation begun 3 days before CsA treatment and continued during the study period (totaling 13 days). In each group (control, CsA alone, CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract alone and black grape alone), there were 7 animals. At the end of the study period, the animals were sacrificed; their kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (xanthine oxidase enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes) parameters were measured in the kidney tissues of the groups. Histopathological examinations of the tissues were also performed. It has been found that CsA creates oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which accelerates oxidation reactions in the kidney tissue. Supplementation with either dried black grape or aqueous garlic extract led to reduced malondialdehyde level in the kidney tissue possibly, by preventing oxidant reactions. In conclusion, the results suggest that impaired oxidant/antioxidant balance may play part in the CsA-induced nephrotoxicity, and some foods with high antioxidant power may ameliorate this toxicity, in agreement with studies with antioxidant vitamins.
  Immunological investigations 02/2007; 36(1):105-14.
• Article: Vanadate-induced inhibition of BCR-triggered apoptosis is coupled with tyrosine phosphorylation and induction of G2M growth arrest in Ramos-BL B cells.

  Kroum K Hristov, Kirstine A Knox, Vanio I Mitev
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  ABSTRACT: The regulation of the tyrosine phosphorylation of key signaling molecules by tyrosine kinases and phosphatases is essential for BCR-triggered signaling cascades during B cell selection process. We used the non-selective tyrosine phosphatase inhibitor vanadate to study the importance of the late regulation of the tyrosine phosphorylation for BCR-triggered G1 growth arrest and apoptosis in Ramos-BL B cells. Vanadate induces G2M growth arrest in a dose-dependent manner and prevents BCR-triggered apoptosis. Vanadate-induced upregulation of the tyrosine phosphorylation is concomitant with increased expression of cyclin B and inhibition of caspase-3 activation and PARP cleavage. The anti-apoptotic effect of vanadate was observed even when added up to 6 hours after the treatment of Ramos-BL B cells with anti-IgM. Vanadate increases BCR-triggered tyrosine phosphorylation of the cytosolic tyrosine phosphatases, SHP-1 and SHP-2 after 24 hours. Co-stimulation with anti-CD40 prevents anti-IgM-triggered tyrosine phosphorylation of these phosphatases and up-regulates the expression of SHP-1. We conclude that the regulation of the tyrosine phosphatase activity is indispensable for BCR-triggered execution of the apoptosis in Ramos-BL B cells.
  Immunological investigations 02/2007; 36(3):293-306.
• Article: The role of alveolar macrophages in the pathogenesis of aspiration pneumonitis.

  Nader D Nader, Peter S McQuiller, Krishnan Raghavendran, R N Spengler, Paul R Knight
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  ABSTRACT: A robust TNFalpha response is seen following aspiration of food particles, while there is only a modest response to acid. To examine the direct effects of acid and particulate components of gastric content on local and systemic macrophages. Pathogen-free Long-Evans rats were injured with intratracheal instillation of normal saline (SHAM), low pH saline (ACID), small non-acidic particles (SNAP) or acidified particles (CASP). The alveolar (local) and the peritoneal (systemic) macrophages were harvested following the injury. We examined the phagocytic activity and TNFalpha release by the alveolar and peritoneal macrophages following in vivo and in vitro exposure to acid and/or food particles. TNFalpha release by macrophages was examined in response to E. coli lipopolysaccharide (LPS) stimulation. In rats injured with gastric particles, the number of the mononuclear cells was higher than those obtained from acid-injured animals. Both in vivo and in vitro exposure of the alveolar macrophages to SNAP resulted in increased production of TNFalpha within 8 hours. Transient exposure of the alveolar macrophages to a low pH environment suppressed LPS-induced production of this cytokine. Additionally, the phagocytic activity of the alveolar macrophages was inhibited by in vitro exposure of the macrophages to acid. We conclude that the two components of gastric aspiration have diverse effects on local and systemic macrophages. Although there is a synergy between acid and gastric particulate in producing an acute lung injury, the modulatory effects of these injuries on the alveolar macrophages are averse.
  Immunological investigations 02/2007; 36(4):457-71.
• Article: Insulin-like growth factor-1 receptor RNA expression in hematopoietic stem cell transplanted patients does not correlate with graft-versus-host disease.

  Brigitta Omazic, Ingrid Näsman-Björk, Johan Permert, Inger Lundkvist
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  ABSTRACT: In vivo activated T lymphocytes exhibit altered expression of insulin-like growth factor-1 receptor (IGF-1R) compared to the naïve T lymphocyte pool. The objective of this study was to investigate the expression of IGF-1R RNA in CD4 and CD8 positive cells after allogeneic hematopoietic stem cell transplantation (HSCT) in patients with and without GVHD. For this purpose we isolated RNA from CD4 and CD8 positive cells, sorted with immunomagnetic beads. We used real-time PCR for RNA quantification. We demonstrate a significantly decreased expression of IGF-1R RNA in both CD4 and CD8 positive cells up to 12 months after HSCT. We could not demonstrate a correlation between the IGF-1R RNA expression and T cell activating processes like GVHD, expansion of CD4 or CD8 populations or virus infections.
  Immunological investigations 02/2007; 36(4):493-506.
• Article: Alkylamides from echinacea modulate induced immune responses in macrophages.

  A Matthias, L Banbury, L M Stevenson, K M Bone, D N Leach, R P Lehmann
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  ABSTRACT: The ability of Echinacea and its components to alter the immune response was examined in vitro in a macrophage cell line under either basal or immunostimulated conditions. Potential immunostimulatory and inflammatory activity was determined using a nuclear transcription factor (NFkappaB) expression, tumour necrosis factor alpha (TNFalpha) and nitric oxide (NO) production as biomarkers. In the absence of alternate stimulation, the only significant effects seen were a decrease in NFkappaB expression by a 2-ene alkylamide ((2E)-N-isobutylundeca-2-ene-8,10-diynamide (1)) and a decrease in TNFalpha levels by cichoric acid and an Echinacea alkylamide fraction (EPL AA). When the cells were stimulated by lipopolysaccharide (LPS), inhibition of the increased NFkappaB expression levels was caused by cichoric acid, an Echinacea preparation (EPL), EPL AA and a 2,4-diene ((2E,4E,8Z,10Z)-N-isobutyldodeca-2,4,8,10-tetraenamide (2)). Increases in TNFalpha levels were inhibited by cichoric acid, EPL and EPL AA but enhanced by 1 in the presence of LPS, while only EPL AA was able to inhibit the stimulated increases in NO. When using phorbol myristate acetate to stimulate the cells, NFkappaB and NO levels were unaffected by Echinacea or its components while only cichoric acid and 2 inhibited TNFalpha levels. Although cichoric acid was found to have an effect, it is probably not an important contributor to the Echinacea modulation of the immune response in vivo, as it is not bioavailable. Echinacea appears to attenuate the response of macrophages to an immune stimulus and its combination of phytochemicals exhibits different pharmacological properties to one or more of the isolated major individual components.
  Immunological investigations 02/2007; 36(2):117-30.
• Article: The role of death receptor ligands in shaping tumor microenvironment.

  Theresa L Whiteside
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  ABSTRACT: Death receptor ligands (FasL, TRAIL) activate apoptosis in cells expressing the cognate receptors. Evidence suggests that these ligands also deliver pro-inflammatory signals. In the tumor microenvironment, "Fas counterattack" mounted by tumors against immune cells is mediated by tumor-associated FasL. But death ligands crosslinking their receptors also induce inhibition of apoptosis and activation of the transcription factor, NFkappaB, with a subsequent burst of pro-inflammatory cytokine production and tumor growth promotion. NFkappaB, a key link between inflammation and cancer, regulates dual activities of death ligands, depending on molecular signals in the tumor microenvironment. This paper focuses on death ligands as an example of the extensive repertoire of strategies devised by tumors for escape from immune control.
  Immunological investigations 02/2007; 36(1):25-46.
• Article: Contact activation via ICAM-1 induces changes in airway epithelial permeability in vitro.

  Hyon Choi, Neal W Fleming, Vladimir B Serikov
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  ABSTRACT: The role of ICAM-1 in contact activation of the bronchial epithelial cells is elucidated. Direct contact between epithelial cells and leukocytes is required to change transepithelial electrical resistance (TER) of the epithelium. Migration of human neutrophils across the layers of cultured human airway epithelial cells (Calu-3) or primary cow tracheal epithelial cells was induced by an fMLP gradient. Migrating neutrophils decreased TER and increased permeability to albumin. Monoclonal antibodies to ICAM-1 reduced neutrophil migration, thus reducing the changes in TER and changes in the epithelial permeability to albumin. By confocal microscopy, ERK1/2 was found to be locally activated in the epithelial cells at the sites of migration and cross-linking of ICAM-1. Blockade of ERK1/2 by PD98059 decreased the changes in TER which were induced by ICAM-1 cross-linking. Contact activation of the bronchial epithelial cells, involving ICAM-1 via local activation of ERK1/2, is an important mechanism of alteration of the bronchial epithelial permeability.
  Immunological investigations 02/2007; 36(1):59-72.
• Article: Induction of auto-reactive regulatory T cells by stimulation with immature autologous dendritic cells.

  Yide Jin, Laphalle Fuller, Violet Esquenazi, Bonnie B Blomberg, George W Burke, Gaetano Ciancio, Andreas G Tzakis, Camillo Ricordi, Joshua Miller
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  ABSTRACT: We have shown in ex vivo studies in donor bone marrow-infused kidney transplant recipients, that chimeric cells of either donor or recipient origin taken from the recipient's bone marrow down-regulated the recipient's cellular immune responses. In the present study, we have now induced regulatory T cells from peripheral blood mononuclear cells (PBMC) of renal transplant recipients or laboratory volunteers by multi-stimulation with autologous immature dendritic cell (iDC) enriched populations derived from either bone marrow cells (BMC) of the (immunosuppressed) kidney transplant recipients or PBMC of the laboratory volunteers (i.e., ibDC and ipDC, respectively). These regulatory T cells, induced by ibDC and ipDC, were autoreactive and designated as TAb and TAp with similar phenotypes and functional profiles. They were largely CD4 + CD25high, CD45RA low and CD45RO high, and uniformly expressed intracellular CTLA-4, and message of IL-4, IL-10, Foxp3, and differentially expressed TGFbeta. Their proliferative responses to autologous mature dendritic stimulating cells (mDC) were approximately two-fold stronger than to allogeneic mDC, and to allogeneic mDC were significantly lower than those of (control) autologous TPBL, suggesting an anergic state. TAb and TAp were not cytotoxic to autologous cells expressing Epstein-Barr virus (EBV) antigens, but were able to inhibit (regulate) the effector phase of this TPBL response to both autologous and allogeneic EBV lymphoblasts. This regulation appeared to require cell-to-cell contact.
  Immunological investigations 02/2007; 36(2):213-32.