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J Marcinkiewicz

Publications and source records attributed to J Marcinkiewicz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes.

OBJECTIVE: To examine whether taurine (Tau) or its physiologic chlorinated derivative, taurine chloramine (Tau-CI), affects proliferation of, and proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) production by, fibroblast-like synoviocytes (FLS) isolated from rheumatoid arthritis (RA) patients. METHODS: FLS, isolated from the synovial tissue of 19 RA patients and cultured in vitro for 3-6 passages, were stimulated with the recombinant human cytokines IL-1beta (1 ng/ml), tumor necrosis factor alpha (TNFalpha; 10 ng/ml), or IL-17 (10 ng/ml) in the presence of either Tau or Tau-Cl, which were added at concentrations of 50-500 microM. Tau and Tau-Cl were added simultaneously with, 2 hours before, or 24 hours after the stimuli. The concentrations of IL-6 and IL-8 were determined in culture supernatants using specific enzyme-linked immunosorbent assays. Proliferation of FLS was estimated on the basis of 3H-thymidine incorporation into the cells, which were cultured for 72 hours in the presence of recombinant human basic fibroblast growth factor (bFGF) (1 ng/ml) and Tau or Tau-Cl, which were added simultaneously at the beginning of the culture. RESULTS: Cultured in vitro, RA FLS spontaneously secreted low levels of IL-6 and IL-8, but when RA FLS were stimulated with IL-1beta, TNFalpha, or IL-17, significantly higher amounts of IL-6 and IL-8 were produced. Tau-Cl, but not Tau, inhibited cytokine-triggered synthesis of IL-6 (50% inhibitory concentration [IC50] approximately 225 microM) and IL-8 (IC50 approximately 450 microM) when added simultaneously with the stimuli. However, IL-17-induced production of IL-8 was not affected by Tau-Cl. In the cells prestimulated with IL-1beta for 24 hours, Tau-Cl still inhibited synthesis of IL-6, but did not affect IL-8 production. Moreover, Tau-Cl inhibited spontaneous and bFGF-triggered proliferation of FLS in a dose-dependent manner. Neither Tau nor Tau-Cl affected cell viability. CONCLUSION: The results of these studies demonstrate that Tau-Cl inhibits production of proinflammatory cytokines by RA FLS, as well as proliferation of these cells. Thus, Tau-Cl may act as a physiologic modulator of FLS functions related to their pathogenic role in RA.

Adult↗
PubMed1999

Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system.

Taurine chloramine (TauCl) is a major chloramine generated in activated neutrophils as a result of the reaction of highly toxic hypochlorous acid and taurine, the most abundant free amino acid in cytosol. In this study we have tested the influence of TauCl on the properties of murine dendritic cells (DC), the major cell population involved in the initiation of an adaptive immune response against pathogenic organisms. N418+, MHC II+, B7-2+ dendritic cells, generated from the mouse bone marrow cells cultured in the presence of granulocyte-macrophage colony-stimulating factor, were stimulated by interferon-gamma and lipopolysaccharide to produce nitric oxide, reactive oxygen species, interleukin-6 (IL-6), tumour necrosis factor-alpha, and IL-12, in the presence of different doses of TauCl. TauCl differently inhibited the generation of these inflammatory mediators in a dose-dependent manner. Furthermore, TauCl selectively modulated the ability of DC to induce the release IL-2 and IL-10 from T cells. These results suggest that neutrophil-derived mediators, such as TauCl, at a site of inflammation, may affect the functions of sentinel DC and macrophages, and play a role in maintaining the balance between the inflammatory response and the induction of an antigen-specific immune response.

Animals↗
PubMed1998

The pro-protein convertase PC1 is induced in the transected sciatic nerve and is present in cultured Schwann cells: comparison with PC5, furin and PC7, implication in pro-BDNF processing.

Injury of peripheral nerves induces expression of several pro-protein convertases (PCs) involved in processing of precursor proteins into their diverse active end-products. In this study, the focus was on convertase PC1 which, although undetectable in control nerves, is strongly induced in injured nerves. High concentrations of PC1 mRNA of 9.0, 5.5, 3.0, 2.5 and 1.6 kb were observed on day 4 post-lesion in proximal and distal segments. By in situ hybridization PC1 mRNA was detected in most of endoneurial cells, which were further identified by immunocytochemistry as myelin 2', 3'-cyclic nucleotide 3'-phosphodiesterase containing Schwann cells. PC1 mRNA and protein were also present in cultured Schwann cells also containing convertases PC5, furin and PC7 as well as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Mostly unprocessed pro-NGF of 35 kDa and pro-BDNF of 35 kDa were found on Western blotting of Schwann cells. Expression of exogenous neurotrophins by infection with vaccinia virus vector showed that mouse pro-NGF and rat pro-BDNF are cleaved intracellularly on smaller forms of 13.5 kDa NGF and 14 kDa BDNF. Infection experiments demonstrated that Schwann cells contain active processing enzymes. In conclusion, this work provides in vivo evidence of the presence of several PCs in the injured rat sciatic nerve and ex vivo in cultured Schwann cells.

Animals↗
PubMed1998

Taurine chloramine down-regulates the generation of murine neutrophil inflammatory mediators.

We previously reported that taurine chloramine (TauCl), a product of activated neutrophils, inhibits the generation of macrophage inflammatory mediators such as nitric oxide (NO), TNF-alpha, and PGE2. Taurine, the most abundant free amino acid in the cytosol of neutrophils, is chlorinated to form TauCl by the halide-dependent myeloperoxidase (MPO) system. Under physiological conditions, TauCl reduces HOCl toxicity. In this study, we investigated the influence of TauCl on generation of oxygen free radicals, cytokines and eicosanoids by activated murine peritoneal neutrophils. We found that TauCl, but not taurine alone, inhibited the production of NO, prostaglandin E2, interleukin-6 and tumor necrosis factor-alpha, in a dose-dependent manner. In contrast, the products of the respiratory burst, as measured by luminol-dependent chemiluminescence (LCL), were reduced by both taurine and TauCl. However, taurine affected LCL at higher concentrations and to a lesser extent than TauCl. The results of these studies suggest that TauCl decreases production of tissue-damaging inflammatory mediators and may regulate the balance between protective, microbicidal and toxic effect of neutrophils.

Animals↗
PubMed1998

Modulation of antigen-specific T-cell activation in vitro by taurine chloramine.

Taurine chloramine (TauCl) is produced during inflammation by reaction of hypochlorous acid (HOCl) with taurine, the most abundant free amino acid in neutrophils. We previously reported that TauCl inhibits the generation of macrophage inflammatory mediators such as nitric oxide, prostaglandin E2 (PGE2), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In this study, the activity of TauCl in modulating T-cell activation was investigated. Treatment of T cells with TauCl (0.1-0.3 mM), prior to activation, was found to inhibit interleukin-2 (IL-2) release in response to both mitogen and antigen stimulation. Similarly, pretreatment of A-20 antigen presenting cells (APCs), at low cell numbers, was found to inhibit their ability to process and present ovalbumin (OVA) to a specific T-cell hybridoma. In contrast, pretreatment of higher numbers of A-20 cells with TauCl in the presence of OVA enhanced subsequent presentation of OVA. Finally, OVA modified with TauCl was processed and presented more efficiently than native OVA. Thus, TauCl is able to modulate induction of a specific adaptive immune response at several independent points of the overall antigen-presenting pathway.

Animals↗
PubMed1998

[Immunoregulatory mechanisms of action of intravenous gammaglobulin in Kawasaki syndrome].

Kawasaki Syndrome (KS) is an acute vasculitis in young children associated with the development of coronary artery abnormalities. KS has been reported to occur in over 40 countries including Poland. The etiology of this disease remains controversial. However, recent studies suggest a potential role of bacterial toxins (superantigens) in the immunopathogenesis of KS. Immunomodulatory benefit and potential toxin neutralisation by intravenous immune globulin (IVIG) support the hypothesis of superantigen-related activation of the immune system in KS. The prevalence of cardiovascular abnormalities can be significantly reduced by treating patients during the first 10 days of illness with high-dose of intravenous gammaglobulin. The following predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in Kawasaki and other immune-mediated diseases: (i) functional blockade of Fc receptor on monocytes/macrophages; (ii) modulation of the production of cytokines and cytokine antagonists; (iii) inhibition of complement mediated damage; (iv) neutralisation of bacterial toxins by specific antibodies; (v) neutralisation of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG. These observations provide an important information that early recognition and prompt treatment of this illness is critical for a successful outcome.

Child↗
PubMed1997

Nitric oxide and antimicrobial activity of reactive oxygen intermediates.

It is well documented that nitric oxide contributes to the bactericidal activities of phagocytes. Murine activated neutrophils and macrophages produce both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). However, only neutrophils in the presence of myeloperoxidase, produce an antimicrobial agent, hypochlorous acid (HOCl). Complex interactions of RNI (nitric oxide) with other antimicrobial agents of phagocytes are likely to exist, but these have not been clearly demonstrated. In this study, we treated bacteria (Escherichia coli) with the NO donor, S-nitrosoglutathione (GSNO) and hydrogen peroxide (H2O2) or HOCl. We found that exposure to H2O2 of the bacteria tested resulted in minimal toxicity. However the killing activities of H2O2 were potentiated by GSNO. On the contrary, the NO-donor completely abolished the bactericidal activity of HOCl. Our results indicate that NO-donating drugs in non toxic concentrations used for experimental purposes may strongly affect the cytotoxic activity of neutrophils and macrophages. We suggest that the similar interactions may exist at sites of inflammation.

Anti-Bacterial Agents↗
PubMed1997

Neutrophil chloramines: missing links between innate and acquired immunity.

Neutrophils are the major cellular component of the acute inflammatory response. By contrast, macrophages are the major cellular component in most chronic immunological responses, and act as key regulators of the specific acquired response. Here, Janusz Marcinkiewicz examines recent data indicating that chloramines, the neutrophil-specific products of the myeloperoxidase--hydrogen-peroxide--halide system, may provide a bridge between the afferent branches of the innate and acquired immune response.

Animals↗
PubMed1997

Enhancement of CD4+ T-cell-dependent interleukin-2 production in vitro by murine alveolar macrophages: the role of leukotriene B4.

Local tissue macrophages are known to play a key role in regulation of adaptive immune responses, often by inhibition of T-cell activation and proliferation. In this study, we compare the influence of alveolar and peritoneal macrophages on T-cell-dependent interleukin-2 (IL-2) release. Alveolar macrophages, in contrast to peritoneal macrophages, enhance IL-2 release. Assay of a panel of potential macrophage-derived mediators indicated that activated alveolar macrophages stimulated greater release of IL-1 beta, tumour necrosis factor-alpha and, especially, leukotriene B4 (> 100 times) than activated peritoneal macrophages. Inhibition of prostaglandin synthesis by alveolar macrophages further enhanced the production of IL-2, while inhibition of leukotriene synthesis abolished the enhancement. The addition of exogenous prostaglandin E2 inhibited IL-2 release, while exogenous leukotriene B4 enhanced IL-2 release. When added simultaneously, the two compounds antagonized each other's activity. In conclusion, this study confirms that alveolar macrophages enhance IL-2 secretion, and suggests that this enhancement may be due at least in part to the very high rates of production of leukotriene B4. The overall influence of macrophage populations on T cells in vivo will reflect the complex balance between the multiple mediators produced within the local tissue microenvironment.

Animals↗
PubMed1997

Regulation of cytokine production by eicosanoids and nitric oxide.

Cytokines are widely regarded as regulatory molecules of inflammatory and immune reactions. Nevertheless, the details of functioning of the complex cytokine network are not yet fully understood. Recent data indicate that eicosanoids, primarily the products of the inducible form of cyclooxygenase (COX-2), are involved in the regulation of cytokine production. We have shown that prostaglandins of E series are no longer only suppressor molecules but they selectively up- or down-regulate the cytokine production. Similarly, nitric oxide (NO) generated in activated immune cells by inducible isoform of nitric oxide synthase (iNOS), is considered to be an immunoregulatory molecule. In this article we present a new concept of interactions between cytokines, eicosanoids (prostaglandins and leukotrienes) and NO. Finally, the impact of these molecules on the regulation of the immune system is discussed.

Animals↗
PubMed1996

Is there a role for nitric oxide in regulation of T cell secretion of IL-2?

Nitric oxide (NO) can have both effector (cytotoxic) and regulatory roles in immune function. In this study, we have re-examined the potential role of nitric oxide in mediating the macrophage-dependent suppression of IL-2 synthesis. In our model, TNP-specific CD4+ T cells are cocultured with Ag and either peritoneal or alveolar macrophages. Both populations of macrophages after in vitro stimulation with IFN-gamma can inhibit IL-2 release. In vitro stimulation also induces substantial levels of NO release by these macrophages, as well as high levels of prostaglandin E2 (PGE2). However, there was no correlation between NO levels and inhibitory activity. Furthermore, NG-monomethyl-L-arginine monoacetate, a specific inhibitor of NO release had no effect on IL-2 release, while indomethacin, which blocked prostaglandin synthesis, largely abrogated the suppressor activity of both macrophage populations. Although the addition of exogenous NO donors at high concentrations could inhibit IL-2 release by T cells, our data does not support the hypothesis that NO is a major macrophage mediator of suppression in this model.

Animals↗
PubMed1996

Oxidative modification of ovalbumin.

Stimulated neutrophils (PMNL) are a source of the active oxygen species: O2, H2O2 and HOCl/OCl- which in turn can act on proteins yielding a variety of mixed oxidation products. A system is proposed in which a model protein-ovalbumin (OVA) first undergoes chlorination by HOCl/OCl- and next is oxidised by H2O2. The modification of functional groups (-NH2, -SH, -S-S-, > C = O, Tyr and Trp) in OVA was monitored as well as their accessibility to promote aggregation. Chlorination resulted in additional inter- or intra -S-S- bond formation followed by a decrease in the total sulfhydryl group content. Amino groups were oxidised to carbonyl moieties with a concomitant acidic shift of pI. Formation of chlorotyrosine at the chlorination step was confirmed and its further H2O2-mediated transformation to bityrosine was demonstrated. It has also been confirmed that tryptophan, and not tyrosine, is the first target for chlorination. SDS/PAGE and HPLC profiles revealed that HOCl/OCl- chlorination promotes formation of aggregates stabilised by non covalent bonds. In conclusion, we suggest that a dramatic change in the OVA molecule structure begins when the molar excess of HOCl/OCl- is about 2 per one reactive group in OVA.

Chromatography, High Pressure Liquid↗
PubMed1995

Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages.

Nitric oxide (NO) plays a key role in mediating macrophage cytotoxicity towards different targets, including tumoral cells and intracellular pathogens. However, its role in macrophage immunoregulation is less well defined. In this study, we have investigated the effect of altering NO levels on the production by mouse macrophages of cytokines, and reactive oxygen intermediates as measured by luminol-dependent chemiluminescence. Our results demonstrate that NO can enhance the release of both tumor necrosis factor-alpha and interleukin-1 alpha, and chemiluminescence. Thus, in addition to acting as a powerful effector molecule in mediating cytotoxic activities of mouse macrophages, NO can play a role in enhancing the production of a variety of other inflammatory mediators, and thus can contribute both directly and indirectly to the immunopathology of macrophage-dependent inflammation.

Animals↗
PubMed1995

Taurine chloramine, a product of activated neutrophils, inhibits in vitro the generation of nitric oxide and other macrophage inflammatory mediators.

Taurine (Tau) is an exceptionally abundant free amino acid in the cytosol of inflammatory cells and especially in neutrophils. Taurine protects cells from self-destruction during processes that generate oxidants. The major function of Tau in leukocytes is to trap chlorinated oxidants (HOCl). Taurine reacts with HOCl to produce the long-lived compound taurine chloramine (TauCl). Previously, we have shown that other products of the neutrophil chlorinating system are able to modify functions of macrophages. In this study, we investigated in vitro the influence of TauCl on the generation of inflammatory mediators by activated macrophages. We have found that TauCl inhibited the generation of nitric oxide, prostaglandin E2, tumor necrosis factor alpha, and interleukin-6, but TauCl slightly enhanced the release of IL-1 alpha. The formation of nitrites by interferon-gamma-activated macrophages was inhibited by TauCl in a dose-dependent manner. Taurine chloramine also reduced the level of inducible nitric oxide synthase (iNOS) mRNA in macrophages, in a similar concentration-dependent manner. Although our experiments do not exclude a direct effect of TauCl on enzymatic activity of iNOS, the inhibition of iNOS expression seems to be the major mechanism responsible for suppression of NO formation. Finally, we discuss the biological role of TauCl in vivo. We suggest that at the site of inflammation TauCl works as a specific signaling molecule of activated neutrophils that coordinates the generation of inflammatory mediators in macrophages.

Animals↗
PubMed1995

MHC class I and class II determinants and some adhesion molecules are engaged in the regulation of nitric oxide production in vitro by human monocytes stimulated with colon carcinoma cells.

Surface molecules that are involved in tumor-monocyte interactions were studied. The in vitro system in which human blood monocytes are stimulated with human colon carcinoma cells for nitric oxide (NO) production was used. Monoclonal antibodies (mAbs) against various adhesion molecules (LFA-1, ICAM-1, VNR) were unable to block NO production in coculture of monocytes with carcinoma cells. However, anti-CD44, -LFA-3, and -VLA beta 1 chain mAbs effectively blocked NO production. Also mAbs against MHC class I and HLA-DR molecules inhibited, in a dose-dependent manner, No release. It was concluded that some adhesion molecules and MHC class I and/or class II determinants of monocytes may be involved in tumor-monocyte interactions leading to signal transduction for NO production.

Antibodies, Monoclonal↗
PubMed1995

The modulation of IL-2 dependent proliferation of CTLL-2 cells by 2-methyl-thiazolidine-2,4-dicarboxylic acid.

It is known that cysteine and other thiol compounds are able to modulate the immune response. The extracellular concentration of cysteine was shown to determine the intracellular level of glutathione (GSH). Thus cysteine, by enhancing GSH production, is able to affect some T-cell functions like IL-2 dependent cell proliferation and the generation of cytotoxic T cells. However, physiologically blood plasma cysteine is maintained at a very low concentration. The use of cysteine as a therapeutic compound in vivo is strongly limited due to its cytotoxicity. Recent studies demonstrate that N-acetyl-cysteine (NAC) as well as a variety of thiazolidine derivatives (TDs), which are the products of the reaction of L-cysteine with carbonyl compounds, could serve as a 'delivery' system for cysteine into the cell. In the present study, we have shown that 2-methyl-thiazolidine-2,4,-dicarboxylic acid (CP), the product of condensation of L-cysteine and pyruvate, strongly increases the proliferation of one particular cell line, IL-2 dependent CTLL-2 cells. We have also shown that this compound significantly increases the intracellular level of non-protein sulfhydryls (NPSH), but we did not find any correlation between NPSH levels and cell viability and proliferation. In contrast to CP, free cysteine showed its toxic properties by affecting cell viability of different cell lines and also by cancelling the influence of CP on the proliferation of CTLL cells.

Adjuvants, Immunologic↗
PubMed1995

Effect of pentoxifylline on nitric oxide released by murine macrophages.

The growing knowledge on the pathological role of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in septic shock stimulated efforts to control their generation pharmacologically in clinical situations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl-L-arginine (an inhibitor of NO synthase), PTXF influenced NO generation only during the induction phase. In conclusion, we suggest that a possible new therapeutic approach in septic shock may result from the inhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental investigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.

Amino Acid Oxidoreductases↗