N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibits tumour necrosis factor-alpha (TNF-alpha) production on lipopolysaccharide (LPS)-stimulated human neutrophils.

During gram-negative infections bacterial components, such as LPS and formylated peptides, exert profound physiological effects on polymorphonuclear neutrophils (PMN) resulting in increased neutrophil effector activities, including the generation of oxidative metabolites, degranulation, phagocytosis and cytokine release. There is not enough evidence about the relationships between LPS and formylated bacterial peptides in the triggering and regulation of the immune inflammatory response. In this study, we present evidence indicating that pretreatment of human PMN with a prototype formylated peptide such as fMLP results in the inhibition of TNF-alpha secretion, a key molecule that plays a central role in the pathogenesis of septic shock.

Inhibition of Fc gamma R-dependent functions by N-formylmethionylleucylphenylalanine in human neutrophils.

Human polymorphonuclear neutrophils (PMN) participate in different cellular functions, including phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and release of reactive oxygen intermediates. Each of these functions can be triggered by receptors for the Fc portion of IgG molecules (Fc gamma R). Normal resting neutrophils possess Fc gamma RII and Fc gamma RIIIB receptors.

Anti-oxidants inhibit the enhancement of the immune response caused by oil adjuvants.

Adjuvants are agents that can induce strong immunity to different antigens. They are thought to act mainly by stimulating macrophages, causing the release of cytokines, which in turn induce an inflammatory focus necessary for the adjuvant action. The authors found that catalase, ascorbic acid, N-acetylcysteine and glutathione are able to inhibit the enhancing effect of incomplete Freund adjuvant (IFA) and polyoxyethylated castor oil upon the humoral immune response to sheep red blood cells (SRBC).

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients.

Cytotoxic T cells play an important role in host defence mechanisms, as well as in the immunopathology of leprosy. In this study, we evaluated whether Mycobacterium leprae hsp18, hsp65 and Myco. tuberculosis hsp71 could induce cytotoxic T cell activity against autologous macrophages pulsed with these hsp.

Impairment of the murine mononuclear phagocyte system function by antigenic stimulation.

This study examined the mononuclear phagocyte system (MPS) capacity to eliminate IgG-sensitized syngeneic erythrocytes (EA) after antigenic challenge. Survival data of EA in normal and preimmunized mice showed that a single dose of T-dependent antigen was able to delay Fc gamma R-dependent clearance. This impairment in EA elimination was dependent on the dose of antigen injected.

IFN-gamma, IL-6 and IL-4 modulate M. leprae- or PPD-specific cytotoxic T cells in leprosy patients.

Specific cytotoxic T cells against intracellular pathogens may be generated in vitro. On the other hand it is well known that cytokines can regulate almost every aspect of immune function. The aim of this study was to evaluate the effect of some cytokines on the generation of cytotoxic T cells with specificity for Mycobacterium leprae- or PPD-pulsed autologous macrophages from leprosy patients and normal controls.

Extracellular acidic pH modulates oxygen-dependent cytotoxic responses mediated by polymorphonuclear leucocytes and monocytes.

In the present study, we compared the ability of human neutrophils and monocytes to display oxygen-dependent cytotoxic responses at pH 7.4 and 6.2.

T-cell-mediated cytotoxicity against Mycobacterium antigen-pulsed autologous macrophages in leprosy patients.

The involvement of CD4+ T lymphocytes in the defense mechanisms against intracellular pathogens is widely recognized. Little information is available on the generation and specificity of the cytotoxic cells that eliminate human monocytes/macrophages infected with mycobacteria. In this work, we tested whether mononuclear cells from leprosy patients could generate cytotoxic T-cell activity against autologous macrophages pulsed with Mycobacterium leprae or purified protein derivative (PPD) in a 4-h 51Cr release assay.

Interferon-gamma is unable to increase monocyte and neutrophil-mediated nonspecific cytotoxicity induced by immune complexes.

We have previously demonstrated that normal human neutrophils and monocytes triggered by immune complexes (IC) are able to destroy non-sensitized target cells through the activation of a nonspecific cytotoxic mechanism (NSC), that is dependent on the generation of reactive oxygen intermediates (IRO). In the present study, we analyze the ability of interferon-gamma (IFN-gamma) to modulate NSC. Our results indicate that, despite the ability of IFN-gamma to increase both the generation of superoxide anion and hydrogen peroxide by phagocytic cells and the expression of the high-affinity 72-kDa Fc gamma RI, it is completely unable to increase NSC mediated either by neutrophils or monocytes.

Neutrophil-mediated cytotoxicity induced by secretory IgA.

Normal human neutrophils triggered by secretory IgA (sIgA) displayed low levels of cytotoxicity towards non-sensitized red blood cells. Catalase completely impaired this non-specific cytotoxicity (NSC), while superoxide dismutase (SOD) significantly enhanced it, suggesting a key role for hydrogen peroxide (H2O2) in the lysis of target cells. Three heme-enzyme inhibitors, sodium azide, sodium cyanide and 3-amino-1,2,4-triazole, did not decrease NSC, but significantly enhanced it, suggesting that the mechanism involved is not dependent upon myeloperoxidase (MPO).