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iNOS expression and NO production by neutrophils in cancer patients

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Jablonska E., Puzewska W., Marcinczyk M., Grabowska Z.

Archivum Immunologiae et Therapiae Experimentalis

2005

vol. 53

issue 2

175-179

The tumor-polymorphonuclear neutrophil (PMN) relationship can be altered by the release of toxic molecules, such as nitric oxide (NO). The aim of the present study was to examine the expression of the inducible synthase of NO (iNOS) and NO production by human neutrophils of patients with oral cavity cancer. For comparison we performed similar examinations in autologous peripheral blood mononuclear cells (PBMCs). PMNs and PBMCs were isolated from the whole blood of 27 patients with squamous cell carcinoma of the oral cavity. iNOS protein expression in these cells was detected by Western blot. Total nitrite as an indicator of NO concentrations in the culture supernatants and the serum of patients was measured using a colorimetric assay. The PMNs of oral cavity cancer patients showed a significantly lower intensity of iNOS expression than those of healthy controls. The PBMCs of patients showed a more intensive expression of iNOS than the PMNs, but a lower intensity than the PBMCs of the controls. The expression of iNOS in rhIL-6 and rhIL-15-stimulated PMNs and PBMCs of patients increased in comparison with unstimulated cells. We observed lower productions of NO by PMNs and PBMCs of patients than those of the control group. The results revealed that altered iNOS expression and NO production are more characteristic of PMNs than of PBMCs of patients with oral cavity cancer. Additionally, this study provided new information about IL-6 and IL-15 activity in a tumor-bearing host.

Toll-like receptors types 2 and 6 and the apoptotic process in human neutrophils

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Jablonska E., Marcinczyk M., Jablonski J.

Archivum Immunologiae et Therapiae Experimentalis

2006

vol. 54

issue 2

137-142

Introduction: Neutrophils (PMN) apoptosis plays an important role in limiting the last phase of inflammatory processes. It is unknown whether Toll-like receptor (TLR)2 acts independently or together with TLR6 in this process. Materials and Methods: The aim of this study was to estimate the relationship between the expressions of TLR2 and TLR6 and the apoptosis of human neutrophils in physiological conditions. We investigated the influence of recombinant human interleukin (IL)-18 and N-formyl-metionyl-leucyl-phenylalanine (fMLP) on the relationships between these receptors and neutrophil apoptosis. Results: Our results showed that after 4-h incubation, the percentage of apoptotic PMNs significantly increased compared with PMN counts before incubation. The stronger expression of TLR2 on the neutrophils suggests that this receptor contributes more significantly to the induction of PMN apoptosis than does TLR6. We also demonstrated an influence of recombinant human IL-18 (rhIL-18) on the expression of TLR6, whereas this effect was not observed in the expression of TLR2. We observed that both rhIL-18 and fMLP inhibited the apoptosis of PMNs and that rhIL-18 had a stronger effect than fMLP. Conclusions: The obtained results suggest that not only TLR2, but also TLR6 plays an important role in the regulation of the apoptosis of PMNs. Changes in the expression of TLR6 and inhibition of apoptosis of PMNs by rhIL-18 seem to confirm the vital role this receptor and of rhIL-18 in regulating the survival of these cells. These data can be useful in developing methods to regulate PMN apoptosis in conditions associated with their excessive and unfavorable activation.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2006

1 2005

2 Jablonska E.

2 Marcinczyk M.

1 Grabowska Z.

1 Jablonski J.

1 Puzewska W.

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iNOS expression and NO production by neutrophils in cancer patients

Toll-like receptors types 2 and 6 and the apoptotic process in human neutrophils