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J Marcinkiewicz

Publications and source records attributed to J Marcinkiewicz.

At least 55 records · Page 3Linked to original sources
PubMed1994

Human monocytes are stimulated for nitric oxide release in vitro by some tumor cells but not by cytokines and lipopolysaccharide.

Nitric oxide (NO) has been recently identified as a potent mediator of tumoricidal activity of activated macrophages. Macrophages can be activated for tumor cell killing by microbial products, including lipopolysaccharide (LPS) and various cytokines. Here we report that in contrast to mouse macrophages, human peripheral blood monocytes stimulated with cytokines or LPS failed to release NO. Also priming of monocytes with interferon-gamma followed by activation with cytokines or LPS did not cause NO secretion. However, monocytes responded with NO production to stimulation with some human cancer cells but not with untransformed cells. NO production by monocytes was inhibited by NG-monomethyl-L-arginine, specific inhibitor of NO synthase and emetine, an irreversible blocker of protein synthesis. This may imply that human monocytes are unique in their restricted capacity to produce NO following interaction with some tumor cells, but not with other stimulators, and in this respect they may be able to distinguish between malignant and normal cells.

Animals↗
PubMed1994

Cyclophosphamide uncovers two separate macrophage subpopulations with opposite immunogenic potential and different patterns of monokine production.

As shown previously, thioglycollate-induced peritoneal macrophages consist of two subpopulations which differ morphologically and functionally. When tagged with trinitrophenyl hapten (TNP), one macrophage subpopulation induced in vivo effector cells (Th1) of contact sensitivity (CS) reaction, while the other induced suppressor T cells (Ts) which inhibit CS and are highly sensitive to the in vivo action of cyclophosphamide (CY). Our present experiments show that CY-resistant (Th inducers) and CY-sensitive macrophages (Ts inducers) differ also in the spectrum of biologically relevant molecules which they secrete when stimulated by LPS. Thus macrophages which preferentially induce Th1 cells have a cytokine pattern IL-1LOW, IL-6HIGH, TNF-alpha LOW, while macrophages which recruit Ts cells are IL-1HIGH, IL-6LOW, TNF-alpha HIGH. TH1 inducers produced also somewhat better PGE2 then Ts inducers. Production of reactive nitrogen intermediates (NO/NO2-) was similar in both groups of macrophages. The reasons for the differential effect of CY on these two populations is not clear at present, although it is known that CY metabolites can bind to sulfhydryl groups on antigen presenting cells (APC) and thereby up- or downregulate the antigen presenting capacities of separate subpopulations of APC.

Animals↗
PubMed1994

An improved experimental model for the study of in vitro release of nitric oxide by murine peritoneal macrophages.

In the immune system macrophages are the cells responsible for nitric oxide (NO) production. The synthesis of NO by activated macrophages correlates with their cytotoxic effect on neoplastic cells as well as killing of intracellular parasites. In the present paper we test several parameters that may influence (in vitro) NO production by murine peritoneal macrophages previously stimulated in vivo by intraperitoneal injection of thioglycollate. In our system the maximum NO/NO2- release was obtained in the culture containing 10(6) M phi/ml after 24 h incubation. For macrophage activation we used lipopolysaccharide (LPS) and several recombinant cytokines (IFN-gamma, TNF-alpha, IL-2, IL-3, IL-6). We also tested the influence of latex phagocytosis on NO production by simultaneously activated macrophages.

Animals↗
PubMed1994

Differential effects of chlorination of bacteria on their capacity to generate NO, TNF-alpha and IL-6 in macrophages.

Activated rodent macrophages produce high amounts of nitric oxide (NO). NO as a tumoricidal and defence molecule against intracellular parasites is commonly accepted. However, its role as an obligatory killing factor for extracellular bacteria is controversial. In the present study we stimulated murine peritoneal macrophages by heat-killed bacteria (Staphylococcus aureus, S. epidermidis and Escherichia coli). In some groups bacteria were pretreated with HOCl, to replace the chlorinating system in activated neutrophils that operates as a bactericidal system in vivo. High levels of NO, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected after stimulation by all non-chlorinated bacteria strains tested. However, after chlorination Gram-positive bacteria lost their ability to induce NO and TNF-alpha, whereas phagocytosis and IL-6 production were not affected by chlorination.

Animals↗
PubMed1993

Regulation of in vitro release of TH2 type cytokines (IL-4, IL-6) in the T cell response to the trinitrophenyl (TNP) hapten.

We have investigated in vitro the ability of T cells from mice primed for contact hypersensitivity to release cytokines of the TH2 subtype, in particular IL-4 and IL-6. We demonstrate that both these cytokines are indeed produced by T cells from the lymph node and spleen of mice immunized by topical application of picryl chloride and restimulated in vitro by TNP-coupled spleen cells. However, the release of IL-4 is limited by the activity of IFN-gamma, a TH1 cytokine which we have previously shown is also produced after contact sensitization. Finally, induction of tolerance to TNP, by intravenous administration of antigen, or transfer of cells from tolerant mice into naive donors prior to sensitization (which suppresses the contact sensitivity reaction in the recipients) leads to a fall in IL-4 production. Thus neither tolerance nor suppression in this system is mediated by the antagonistic activities of TH1- and TH2-type T cells. In contrast, IL-6 production is upregulated during both suppression and tolerance, suggesting that this cytokine may play a part in the negative regulation of contact sensitivity.

Animals↗
PubMed1993

Differential cytokine regulation by eicosanoids in T cells primed by contact sensitisation with TNP.

Eicosanoids are important mediators of inflammation, but also play a role in regulation of lymphocyte function. In this study we have examined the function of both prostaglandins (PGs) and leukotrienes in regulating the release of a set of cytokines produced by T cells from mice primed with the contact-sensitising agent picryl chloride. Various patterns of response by different cytokines in response to exogenous eicosanoids were observed. Both interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), two cytokines involved in activating the cellular contact sensitivity reaction, were downregulated by prostaglandin E2 (PGE2) and to a lesser extent by 6-keto PGF2 alpha (PGI2). In contrast, both PGE2 and PGI2 potentiated the release of IL-3 and IL-6 which both play an important role in stimulating haemopoesis after inflammation. Unexpectedly, IL-4 release was strongly inhibited by exogenous PGI2, while remaining unaffected by PGE2. This inhibition, in contrast to the PG-mediated effects on IL-2, IL-3, IL-6, and IFN-gamma was not due to increased intracellular levels of cAMP. In contrast to the strong immunomodulatory effects of PGs, leukotrienes B4 and C4 had only small and rather variable effects on any cytokine release.

Animals↗
PubMed1993

Differential regulation of cytokine production by nitric oxide.

Nitric oxide (NO) has recently been identified as a potent and pleiotropic intracellular mediator produced by and acting on many cells of the body. Although considerable attention has been devoted to the regulation of NO by inflammatory cytokines, and also to the role of NO as an important effector molecule in immune function, there is very little information on the role of this mediator in modulating T-cell-dependent cytokine production. In this study we show that physiological levels of NO (either produced by activated macrophages or by the addition of exogenous NO donors) can selectively down-regulate interleukin-3 (IL-3) production by spleen cells from contact-sensitized mice, while leaving IL-2 activity unaffected. Thus NO may have an important role as an immunomodulatory as well as effector molecule in the immune system.

Animals↗
PubMed1992

Enhancement of trinitrophenyl-specific humoral response to TNP proteins as the result of carrier chlorination.

Trinitrophenyl (TNP)-specific humoral response was tested after immunization with TNP-protein conjugates composed of either native proteins or proteins modified by chlorination. Significant enhancement of the hapten-specific response was observed as a result of carrier chlorination. This effect was dose dependent and affected mainly T-helper-cell activation. Since stimulated neutrophils chlorinate in vivo proteins, we propose that they take part in the induction phase of immune response by facilitation of antigen processing and/or presentation.

Animals↗
PubMed1992

Prostaglandin E2 (PGE2) differentially regulates the production of IL-2 and IL-3 by murine immune T-cells.

Eicosanoids are important mediators of inflammation, and have been shown to have potent, and usually suppressive immunoregulatory activities. In the paper, we have examined the role of prostaglandin (PGE2) production in the regulation of two cytokines, IL-2 and IL-3, which both play a key role in contact sensitivity and delayed type hypersensitivity reactions. In agreement with previous studies, we demonstrate that prostaglandins down-regulate IL-2 production in the system. Unexpectedly, however, IL-3 levels are enhanced in the presence of the prostaglandin PGE2 and conversely, are inhibited by treatment with aspirin, a potent inhibitor of prostaglandin metabolism. The implications of this result in terms of the immunoregulatory role of PGs will be discussed.

Animals↗
PubMed1992

In vitro enhanced destruction of erythrocytes as a result of their chlorination.

Subarachnoidal haemorrhage is followed by accumulation of granulocytes and macrophages in cerebrospinal fluid (CSF). As a result erythrocytes are destroyed and removed from CSF. Activated granulocytes chlorinate many species including erythrocytes. It has been shown that chlorinated erythrocytes are more sensitive to phagocytosis by macrophages than the native ones.

Animals↗
PubMed1991

Temperature-induced stress abrogates co-stimulatory function in antigen-presenting cells.

This study examines the effect of heat-induced stress on the function of splenic antigen-presenting cells. Heat shock (at 41 degrees C, 45 degrees C) profoundly inhibits the ability of this population to stimulate antigen-specific proliferation in ex vivo, or short-term cultures of T cells. This inhibition is not due to the release of suppressor factors from the antigen-presenting cells, nor to a lack of interleukin 1. Comparison of the effect of heat shock on presentation to a T cell hybridoma suggest that heat shock may affect the ability of antigen-presenting cells to deliver a co-stimulatory signal to the T cell. The implication of these findings in terms of the regulation of autoimmune phenomena is discussed.

Animals↗
PubMed1991

Influence of no-donor (SIN-1) on functions of inflammatory cells.

NO-donor SIN-1 (0.01-1.0 mM) dose-dependently inhibited the basal and FMLP (30.0 mM)-stimulated release of beta-glucuronidase from rat peritoneal leukocytes and antigen-specific stimulation of Interleukin-2 production by T-hybridomas. I-123 LDL binding to human lymphocytes was inhibited by Iloprost (1 mM) but activated by SIN-1 (0.3 mM). We conclude that beside the smooth muscle cells and platelets the blood inflammatory/immune cells are under the PGI2/NO control, however, the precise regulation as well as physiological importance need further investigation.

Animals↗
PubMed1991

Regulatory responses in contact sensitivity: afferent suppressor T cells inhibit the activation of efferent suppressor T cells.

Two types of suppressor cells regulate the contact sensitivity (CS) response to picryl chloride (PCL). Afferent suppressor T cells (Ts-aff) inhibit the generation of CS responses to PCL, while efferent suppressor T cells (Ts-eff) inhibit the activity of Th 1 cells that mediate CS reaction. Intravenous injection of mice with TNP-substituted peritoneal exudate cells (TNP-PEC) induces Ts-eff cells that block the adoptive transfer of contact sensitivity. The induction of Ts-eff cells is prevented by the presence of Ts-aff cells, which in turn are induced by the injection of TNP-PEC coupled with antibodies of the IgG2a and IgG2b isotype (TNP-PEC-Ab). If an animal is injected with TNP-PEC prior to or simultaneously with TNP-PEC-Ab, it generates only Ts-aff cells, while if it is injected with TNP-PEC alone or TNP-PEC prior to TNP-PEC-Ab, it generates Ts-eff cells. Ts-aff cells effect only the generation of Ts-eff cells, as the addition of Ts-eff cells to assays for Ts-eff cells has no inhibitory effect on the suppressive effects of Ts-eff cells in adoptive transfer. Our experiments show that Ts-aff cells induced by TNP-PEC-Ab are phenotypically either Lyt 1+2- or Lyt 1-2+, but only the latter inhibit the generation of Ts-eff cells in vivo. The Ts-aff cells that inhibit Ts-eff activity adhere to the lectin Vicia villosa (VV), while Ts-eff cells are VV nonadherent. In addition, Ts-aff cells can prevent the generation of Ts-eff to linked haptens presented on the same PEC. It appears that a cascade of Ts cell interactions are involved in the regulation of CS responses.

Animals↗
PubMed1991

In vitro cytokine release by activated murine peritoneal macrophages: role of prostaglandins in the differential regulation of tumor necrosis factor alpha, interleukin 1, and interleukin 6.

Distinct subpopulations of macrophages or differently activated macrophages display various functions in immune reactions. Some of their activities depend on specific sets of factors (i.e., cytokines and eicosanoids) produced by activated macrophages. We have studied the ability of murine (CBA/ca) peritoneal macrophages to selectively release tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and IL-6. We have found that the priming of cells (Mo) with different stimulants (thioglycolate vs. LPS) induces the release of particular cytokines by reactivated macrophages. The increased release of TNF-alpha correlates with lower levels of IL-1 and IL-6. We have also found that prostaglandin E2 (PGE2) and prostacyclin (PGI2) have opposing effects on the production of two of these cytokines. The release of TNF-alpha is inhibited by prostaglandins, whereas increased levels of PGE2 and PGI2 correlate with higher levels of IL-6.

Animals↗
PubMed1991

Immunoadjuvant properties of chitosan.

Adjuvant activity of water insoluble chitosan suspension was examined in CBA mice. Among different types of immune reaction only T-dependent humoral response against SRBC was enhanced by injection of chitosan. The optimal conditions of administration of both agents (antigen-SRBC, adjuvant-chitosan) was established.

Adjuvants, Immunologic↗
PubMed1991

[Immunomodulating properties of Acnevac vaccine].

The influence of Acnevac vaccine on immune responses of CBA mice was tested. Acnevac, the vaccine used in a treatment of patient with acne vulgaris, was produced by a Cracow Sera and Vaccines Manufacturer from cultures of Propionibacteria-strains. It was shown that Acnevac has strong immunomodulatory properties. It strongly stimulates humoral responses, has moderate effect on cell-mediated immune responses and it also activates peritoneal macrophages to release TNF-alpha.

Acne Vulgaris↗