Maciej Tarkowski

Publications of Maciej Tarkowski

• Perinatal exposure of mice to TCDD decreases allergic sensitisation through inhibition of IL-4 production rather than T regulatory cell-mediated suppression.

  Authors: Maciej Tarkowski, Barbara Kur, Marek Nocuń, Krystyna Sitarek

  International journal of occupational medicine and environmental health. 01/2010; 23(1):75-83.

  The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, man-made, persistent organic pollutant with high immunotoxic potentials. It suppresses cell-mediated and humoral immune responsesThe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread, man-made, persistent organic pollutant with high immunotoxic potentials. It suppresses cell-mediated and humoral immune responses through mechanisms dependent on aryl-hydrocarbon receptor expression and immunosuppressive activity of the cells. Most sensitive to TCDD are organisms during fetal and infant life, mostly due to the developmental stage of many biological systems of the host, including immune system. Recent data show that T regulatory cells that have the potential to suppress immune reactions and which develop after TCDD exposure are also responsible for protection from allergy development. Our goal was to investigate if perinatal exposure to TCDD can affect allergic sensitisation and if T reg cells participate in this phenomenon. Mice, Balb/c, were perinatally exposed to TCDD or to the carrier. Six weeks old control or exposed mice were sensitised with ovalbumin. Spleen cells of the animals were used to assess the content of T reg cells by means of flow cytometry. Levels of cytokines were assessed by ELISA technique in supernatants of the cells stimulated with anti-CD3 antibody. As a measure of sensitisation, total IgE and anti-OVA IgE were measured in serum of mice by ELISA method. To assess the function of T reg cells isolated from OVA-sensitised control or TCDD exposed animals we performed transfer studies. Here we show that perinatal exposure to TCDD decreases allergic sensitisation and that this process is related to inhibition of IL-4 synthesis rather than suppression mediated by T regulatory cells. We hypothesise that dioxin exposure can be an important environmental modulator of immunological responses that participate in allergic reactions.

• Comparative studies of lymph node cell subpopulations and cytokine expression in murine model for testing the potentials of chemicals to induce respiratory sensitization.

  Authors: Maciej Tarkowski, Barbara Kur, Ewa Polakowska, Ewa Jabłońska

  International journal of occupational medicine and environmental health. 02/2008; 21(3):253-62.

  Objectives: To investigate immunological changes in lymph nodes based on expression of cell-specific receptors and cytokine expression profile and accompanying inflammatory reactions in lungs of miceObjectives: To investigate immunological changes in lymph nodes based on expression of cell-specific receptors and cytokine expression profile and accompanying inflammatory reactions in lungs of mice treated with chemicals of known potentials to induce respiratory sensitization and those in which activity in this regard is unclear. Materials and Methods: On day 1 and 7, Balb/c mice received toluene-2,4-diisocyanate (TDI), trimellitic anhydride (TMA), 1-chloro-2,4-dinitrobenzene (DNCB), glutaraldehyde (GA), formaldehyde (FA), benzalkonium chloride (ChB) or vehicle. On day 14, they received a single intranasal instillation with the same chemical or vehicle. On day 15, auricular lymph nodes (LN) were excised and used for analyzes of T-, B-cells, expression of CD44 and for the estimation of IL-4 and IFN-gamma production after in vitro stimulation with concanavalin A (ConA) and also for IL-4 and IFN-gamma mRNA expression analyses using Real-Time PCR. Inflammatory changes in lungs were observed by estimation of TNF-alpha and MIP-2 concentrations and cell numbers and their type in BAL. Results: There were no significant changes in cell subpopulations of T helper cells in LN. The percent of B cells was significantly increased after treatment with DNCB, TDI, and GA. Increased expression of CD44 on T cells was also observed. Both IL-4 and IFN-gamma were found increased in TDI- and FA-treated mice, while only IL-4 was increased in TMA-treated mice. Real-Time PCR analyses, however, showed increased IL-4 mRNA expression for TDI- and TMA-, and IFN-gamma mRNA expression for DNCB-treated mice. We haven't observed significant changes in inflammatory reactions in the lungs of exposed animals. Conclusions: Studying immunological changes with first determining the activation status of T cells followed by analyzes of expression of mRNA for Th1 and Th2 cytokines in murine model could be a useful method for assessment of the potentials of chemicals to induce respiratory sensitization but is not sufficient. Addition of ventilatory measurements, but not necessarily inflammatory reactions, could complete the model.

• Immunological determinants of ventilatory changes induced in mice by dermal sensitization and respiratory challenge with toluene diisocyanate.

  Authors: Maciej Tarkowski, Jeroen A J Vanoirbeek, Hadewijch M Vanhooren, Vanessa De Vooght, Caroline M Mercier, Jan Ceuppens, Benoit Nemery, Peter H M Hoet

  American journal of physiology. Lung cellular and molecular physiology. 02/2007; 292(1):L207-14.

  The objective of the study was to characterize better the immunologic mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and severe combined immunodeficiencyThe objective of the study was to characterize better the immunologic mechanisms underlying a previously developed animal model of chemical-induced asthma. BALB/c and severe combined immunodeficiency disease (SCID) mice received toluene diisocyanate (TDI) or vehicle on each ear on day 1 and/or day 7. On day 10, they were intranasally challenged with TDI or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after challenge. Reactivity to methacholine was measured 23 h later: enhanced pause and actual resistance measurements. Pulmonary inflammation was assessed 1, 6, and 24 h after challenge by bronchoalveolar lavage (BAL). Tumor necrosis factor-alpha and macrophage inflammatory protein (MIP)-2 levels were measured in BAL. Immunological parameters included total IgE, IgG1, and IgG2a in serum, lymphocyte populations in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in supernatants of lymph node cells, cultured with or without concanavalin A. Ventilatory changes suggestive of airway obstruction and increased methacholine reactivity were observed in all TDI-sensitized and TDI intranasally instilled mice, except in SCID mice. A neutrophil influx, accompanied by an increase in MIP-2 levels, was found in BAL of all responding groups 6 and 24 h after intranasal challenge. In BALB/c mice an increased level of CD19+ B cells was found in the auricular lymph nodes. IL-4 and IFN-gamma levels were increased in supernatants of concanavalin A-stimulated auricular lymph node cells from BALB/c mice completely treated with TDI. These results indicate that our model is dependent on the presence of lymphocytes, but it is not characterized by a preferential stimulation of Th1 or Th2 lymphocytes.

• Validation of a mouse model of chemical-induced asthma using trimellitic anhydride, a respiratory sensitizer, and dinitrochlorobenzene, a dermal sensitizer.

  Authors: Jeroen A J Vanoirbeek, Maciej Tarkowski, Hadewijch M Vanhooren, Vanessa De Vooght, Benoit Nemery, Peter H M Hoet

  The Journal of allergy and clinical immunology. 06/2006; 117(5):1090-7.

  BACKGROUND: Occupational asthma can be caused by chemicals. Previously, we established a murine model of immunologically mediated chemical-induced asthma using toluene diisocyanate. OBJECTIVE: WeBACKGROUND: Occupational asthma can be caused by chemicals. Previously, we established a murine model of immunologically mediated chemical-induced asthma using toluene diisocyanate. OBJECTIVE: We sought to verify this model using trimellitic anhydride (TMA), a respiratory sensitizer, and 1-chloro-2,4-dinitrobenzene (DNCB), a dermal sensitizer. METHODS: BALB/c mice received dermal applications (vehicle or chemical) on days 1 and 7. On day 10, they received an intranasal instillation (vehicle or chemical). Whole-body plethysmography (enhanced pause) was used to monitor changes in ventilatory function and methacholine reactivity. Pulmonary inflammation was assessed by using bronchoalveolar lavage (cells, TNF-alpha levels, and macrophage inflammatory protein 2 levels). Immunologic parameters included total serum IgE levels, lymphocyte distribution in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in supernatants of lymph node cells incubated with or without concanavalin A. RESULTS: Mice dermally treated and intranasally challenged with TMA experienced markedly increased enhanced pause immediately after intranasal challenge and increased methacholine reactivity (24 hours later). Mice similarly treated with DNCB did not show any ventilatory changes. Neutrophil influx and increased macrophage inflammatory protein 2 and TNF-alpha levels were found in bronchoalveolar lavage fluid in both TMA- and DNCB-treated mice. The proportion of CD19+ B cells was increased in auricular and cervical lymph nodes of TMA-treated mice. IL-4 and IFN-gamma levels were increased in supernatants of concanavalin A-stimulated auricular and cervical lymph node cells of TMA- or DNCB-treated mice; however, the relative proportions of IL-4 and IFN-gamma levels differed between TMA- and DNCB-treated mice. Serum total IgE levels were increased in TMA-treated mice only. CONCLUSION: Both compounds induce a mixed T(H)1-T(H)2 response, but only TMA induced ventilatory changes. CLINICAL IMPLICATIONS: In the workplace avoiding skin contact with chemical sensitizers might be advised to prevent chemical-induced asthma.

• Occupational asthma caused by cobalt chloride in a diamond polisher after cessation of occupational exposure: a case report.

  Authors: Anna Krakowiak, Wojciech Dudek, Maciej Tarkowski, Sylwia Swiderska-Kiełbik, Ewa Nieścierenko, Cezary Pałczyński

  International journal of occupational medicine and environmental health. 02/2005; 18(2):151-8.

  OBJECTIVES: The inspiration of cobalt containing dust leads to various respiratory symptoms, including asthma and interstitial lung disease. Occupational asthma caused by cobalt chloride has beenOBJECTIVES: The inspiration of cobalt containing dust leads to various respiratory symptoms, including asthma and interstitial lung disease. Occupational asthma caused by cobalt chloride has been diagnosed in a 35-year-old patient, who worked as a diamond polishing disc former. The patient presented a 2-year history of dyspnea, cough and symptoms of rhinitis. MATERIALS AND METHODS: The patient underwent a medical history interview, skin prick tests with common and occupational allergens (cobalt and nickel chloride), and pulmonary function testing both before and after the nasal provocation with 0.05% cobalt chloride. Additionally, the authors analyzed morphological and biochemical changes before and after the specific nasal challenge test. Cell proliferation analysis was also carried out. RESULTS: Skin prick tests (SPTs) with common environmental allergens were found to be negative, while SPTs with cobalt chloride were positive for all applied solutions. The provocation with cobalt chloride caused a significant increase in the proportion of eosinophils, basophils and albumin during the late allergic reaction. The positive lymphocyte transformation caused by cobalt was also observed. CONCLUSIONS: Cobalt salts may induce occupational asthma. The mechanism of this asthma may be IgE-mediated. The cobalt-sensitized lymphocytes may play an important role in this disease.

• Respiratory response to toluene diisocyanate depends on prior frequency and concentration of dermal sensitization in mice.

  Authors: Jeroen A J Vanoirbeek, Maciej Tarkowski, Jan L Ceuppens, Erik K Verbeken, Benoit Nemery, Peter H M Hoet

  Toxicological sciences : an official journal of the Society of Toxicology. 09/2004; 80(2):310-21.

  Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weightOccupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weight chemicals to cause asthma, we verified that dermal sensitization prior to intranasal challenge influences the respiratory response using toluene diisocyanate (TDI), a known respiratory sensitizer. BALB/c mice received TDI or vehicle (acetone/olive oil) on each ear on three consecutive days (days 1, 2, and 3; 0.3 or 3% TDI) or only once (day 1, 1% TDI). On day 7, the mice received similar dermal applications of vehicle or the same concentration of TDI as before ("boost"). On day 10, they received an intranasal dose of TDI (0.1%) or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after intranasal application, and reactivity to inhaled methacholine was assessed 24 h later. Pulmonary inflammation was assessed by bronchoalveolar lavage and histology. Mice that received an intranasal dose of TDI without having received a prior dermal application of TDI did not exhibit any ventilatory response or inflammatory changes compared to vehicle controls. In contrast, mice that had received prior application(s) of TDI, even if only on day 7, exhibited the following: ventilatory responses, compatible with bronchoconstriction, immediately after intranasal application with TDI; enhanced methacholine responsiveness 24 h later; and pulmonary inflammation characterized by neutrophils. This was, however, not the case in mice that received the highest dermal amount of TDI (3% on days 1, 2, and 3). These findings suggest that respiratory response to TDI depends on prior frequency and concentration of dermal sensitization in mice.

• The lymphocytic cholinergic system and its modulation by organophosphorus pesticides.

  Authors: Maciej Tarkowski, Waldemar Lutz, Sarah Birindelli

  International journal of occupational medicine and environmental health. 02/2004; 17(3):325-37.

  Clinical and basic mechanism observations reveal interactions between neural and immune systems. These two systems create a complex network for recognizing danger to the host and its protection fromClinical and basic mechanism observations reveal interactions between neural and immune systems. These two systems create a complex network for recognizing danger to the host and its protection from outside pathogenic elements as well as from inside overreactions of inflammatory character. Here, we review the interactions of these two systems in relation to the effects of pesticides that clearly involve elements of cholinergic lymphocytic system. We discuss cellular and soluble elements of the immune system, which may be affected by pesticide exposure. We suggest that in-depth studies of the influence of pesticides on lymphocytes may contribute to the development of sensitive methods of measuring early adverse effects appearing in response to pesticide exposure.

• Expression and a role of CD30 in regulation of T-cell activity.

  Authors: Maciej Tarkowski

  Current opinion in hematology. 08/2003; 10(4):267-71.

  CD30 receptor has been known for almost 20 years, but its expression and activity are still the subject of many investigations. Its expression was found in different malignancies, and most of theCD30 receptor has been known for almost 20 years, but its expression and activity are still the subject of many investigations. Its expression was found in different malignancies, and most of the studies regarding CD30 focus on its role in lymphomas. The progress that has already been made in this field is reflected in implementation of CD30 as a target for immunotoxin, which has been tested in phase I study in treating Hodgkin lymphoma. CD30 is present also on normal, activated T cells of all cytokine profiles. However, increased density of CD30 and CD30-mediated Th2 cytokine production provide evidence of its role in determining the activity of T cells toward synthesis of cytokines and involvement in reactions of Th2 characteristics. Pleiotropic signaling mediated by CD30 does not implicate this receptor just as a cytokine costimulator; it proves to be important in several different activities of T cells.

• CD30 expression on allergen- and non-allergen-specific T cell lines and its role in cytokine production.

  Authors: Maciej Tarkowski

  Archivum immunologiae et therapiae experimentalis. 02/2003; 51(5):335-43.

  Interest in CD30 has mainly focused on its ability to discriminate between T helper (Th)2 and Th1 subpopulations. The role of CD30 as the marker for Th2 cells is still controversial, which may be dueInterest in CD30 has mainly focused on its ability to discriminate between T helper (Th)2 and Th1 subpopulations. The role of CD30 as the marker for Th2 cells is still controversial, which may be due to the fact that the expression and the role of CD30 is not fully understood. The data presented in this paper provides information on the expression and activity of CD30 in T cell lines specific to allergen or tuberculin-purified protein derivative (PPD) as the model of Th2 or Th1 responses, respectively. The results have shown that CD30 expression was the highest on T cells stimulated with antigen in the presence of interleukin (IL)-12 and it was present on both cell lines, regardless of antigen specificity. Activation of the CD30 receptor on CD4+ T cells, however, showed differences in mRNA expression for IL-4 between these cells. IL-4 mRNA was induced by CD30 costimulation at the same level as was obtained with anti-CD28 agonistic antibodies in allergen-specific T cells. In PPD-specific T cells this effect was not observed. Additionally, there was no effect of anti-CD30 stimulation on IL-6 mRNA expression in any of the cell lines. Comparison of protein cytokine levels for IL-4 and interferon (IFN)-gamma have shown that the highest production of IL-4 was obtained from allergen-specific T cells costimulated with anti-CD28. Although this effect was much lower in the case of CD30 costimulation, it was still above that of anti-CD3 activation alone. No effect of CD30 activation was observed in regard to IFN-gamma mRNA or protein expression in any cell line. The results of the study showed that the CD30 receptor is not exclusively present on Th2 cells; however, its activity may promote a Th2-dependent reaction by modulating IL-4 production.