Jacek M Witkowski

Publications (102) View all

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  Available from: Katarzyna Aleksandra Lisowska

  Article: Hemodialysis affects phenotype and proliferation of CD4-positive T lymphocytes.

  Katarzyna A Lisowska, Alicja Dębska-Ślizień, Aleksandra Jasiulewicz, Zbigniew Heleniak, Ewa Bryl, Jacek M Witkowski
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  ABSTRACT: CD4(+) T lymphocytes of patients with chronic kidney disease (CKD) are characterized by reduced levels of crucial surface antigens and changes in the cell cycle parameters. Recombinant human erythropoietin (rhEPO) normalizes their altered phenotype and proliferative capacity. Mechanisms leading to the deficient responses of T lymphocytes are still not clear but it is postulated that immunological changes are deepened by hemodialysis (HD). Study of activation parameters of CD4(+) T lymphocytes in hemodialyzed and predialysis CKD patients could bring insight into this problem. Two groups of patients, treated conservatively (predialysis, PD) and hemodialyzed (HD), as well as healthy controls, were included into the study; neither had received rhEPO. Proportions of main CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)CD95(+), and CD4(+)HLA-DR(+) lymphocyte subpopulations and proliferation kinetic parameters were measured with flow cytometry, both ex vivo and in vitro. No differences were seen in the proportions of main CD4(+) lymphocyte subpopulations (CD4(+)CD28(+), CD4(+)CD25(+), CD4(+)HLA-DR(+), CD4(+)CD69(+), CD4(+)CD95(+)) between all examined groups ex vivo. CD4(+) T lymphocytes of HD patients exhibited significantly decreased expression of co-stimulatory molecule CD28 and activation markers CD25 and CD69 after stimulation in vitro when compared with PD patients and healthy controls. HD patients showed also decreased percentage of CD4(+)CD28(+) lymphocytes proliferating in vitro; these cells presented decreased numbers of finished divisions after 72 h of stimulation in vitro and had longer G0→G1 time when compared to healthy controls. CD4(+) T lymphocytes of PD patients and healthy controls were characterized by similar cell cycle parameters. Our study shows that repeated hemodialysis procedure influences phenotype and proliferation parameters of CD4(+) T lymphocytes.
  Journal of Clinical Immunology 02/2012; 32(1):189-200. · 3.08 Impact Factor
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  Available from: Jacek M Witkowski

  Article: Beta-amyloid peptides enhance the proliferative response of activated CD4CD28 lymphocytes from Alzheimer disease patients and from healthy elderly.

  Agnieszka Jóźwik, Jerzy Landowski, Leszek Bidzan, Tamas Fülop, Ewa Bryl, Jacek M Witkowski
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  ABSTRACT: Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4(+) and CD8(+) cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4(+)CD28(+) population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4(+)CD28(+) cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4(+) cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.
  PLoS ONE 01/2012; 7(3):e33276. · 4.09 Impact Factor
• Article: Impact of radiofrequency ablation on PBMC subpopulation in patients with renal cell carcinoma.

  Marcin Matuszewski, Jerzy Michajłowski, Igor Michajłowski, Katarzyna Ruckermann-Dizurdzińska, Jacek M Witkowski, Wojciech Biernat, Kazimierz Krajka
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  ABSTRACT: With the development of diagnostic techniques, renal cell carcinoma (RCC) is currently diagnosed in earlier stages, allowing the introduction of less invasive techniques in its management. One of the most promising new treatment methods is based on the utilization of high temperature created by radiofrequency current circulating around the needle probe introduced into the tumor. Besides the direct destruction of the cancer tissue, the treatment may induce immunologic reaction to tumor antigens released from destroyed tumor cell. This paper describes changes observed in the peripheral blood lymphocyte population after radiofrequency ablation (RFA) of RCC. Blood was tested before, and 2, 4, and 6 weeks after the RFA in 6 patients with RCC for the proportions and numbers of CD3(+), CD3(+)HLA-DR(+), CD3(+)CD4(+), CD3(+)CD8(+), and CD56(+)CD16(+) cells. The blood was stained with fluorochrome-conjugated monoclonal antibodies and percentages of cells expressing various markers were determined by flow cytometry. In all patients, the changes were most pronounced 2 weeks after the procedure. The proportion of CD4(+) and CD8(+) lymphocytes were changed. In 1 patient, an increase in both CD4(+) and CD8(+) cells was observed. In 5 out of 6 patients, the proportion of activated (DR(+)) cells was increased over the whole follow-up period with the highest values in the second week after RFA. The percentage of the CD56(+)CD16(+) was decreased in most of the patients. Our study confirms that in the majority of patients, RFA of the renal tumors causes significant changes in the proportion of the peripheral immune cells. We suggest that the results presented in this article shows the necessity for further studies.
  Urologic Oncology 11/2011; 29(6):724-30. · 3.22 Impact Factor
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  Available from: Jacek M Witkowski

  Article: Conventional calpains and programmed cell death.

  Paulina Łopatniuk, Jacek M Witkowski
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  ABSTRACT: The evidence on the crucial role of a family of calcium-dependent cysteine proteases called calpains in programmed cell death is rich and still growing. However, understanding of the mechanisms of their functions in apoptosis is not full yet. Calpains have been implicated in both physiological and pathological cell death control, especially in various malignancies, but also in the immune system development and function. There is also growing evidence on calpain involvement in apoptosis execution in certain pathological conditions of the central nervous system, in cardiovascular diseases, etc. Understanding of the clinical significance of calpain activation pathways, after intense studies of the influence of calpain activity on drug-induced apoptosis, seems especially important lately, as calpains have become noticed as potential therapeutic targets. To allow pharmacological targeting of these enzymes, thorough knowledge of their patterns of activation and further interactions with already known apoptotic pathways is necessary. A comprehensive summary of both well established and recently obtained information in the field is an important step that may lead to future advances in the use of calpain-targeted agents in the clinic.
  Acta biochimica Polonica 08/2011; 58(3):287-96. · 1.49 Impact Factor
• Article: Two systemic lupus erythematosus (SLE) global disease activity indexes--the SLE Disease Activity Index and the Systemic Lupus Activity Measure--demonstrate different correlations with activation of peripheral blood CD4+ T cells.

  Agnieszka Daca, Zenobia Czuszyńska, Zaneta Smoleńska, Zbigniew Zdrojewski, Jacek M Witkowski, Ewa Bryl
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  ABSTRACT: Global disease activity measurement in systemic lupus erythematosus (SLE) patients is important for the clinical estimation and adjustment of therapy. By contrast, immune system activation plays a significant role in disease pathogenesis, with CD4+ lymphocytes acting as central cells in the immune response. We investigated which scale better correlates with immunologic changes in the blood of SLE patients, the SLE Disease Activity Index (SLEDAI) or the Systemic Lupus Activity Measure (SLAM) scale. Samples of peripheral blood were obtained from 45 SLE patients with different disease activity as assessed by the SLEDAI and the SLAM scales on the same day. We assessed the percentage of CD4+ T cells with activation-associated receptors: CD69, CD25int, CD95, HLA-DR, and CD4+ T cells with killing properties containing perforin and granzyme B. Our results indicated that the percentage of CD4+CD69+ and CD4+CD25(int) cells did not correlate with either the SLEDAI or the SLAM scale. Significant and positive correlations were observed between percentages of CD4+CD95+ and CD4+HLA-DR+ lymphocytes and SLE activity, but only when activity was measured using the SLAM scale, not with the SLEDAI scale. The percentage of CD4+perforin+ and CD4+granzyme B+ cells also strongly correlated with disease activity measured only with the SLAM scale. We conclude that the SLAM scale better reflects changes of immune system activity in SLE patients compared with the SLEDAI scale.
  Human immunology 08/2011; 72(12):1160-7. · 2.55 Impact Factor