Interactions between synthesis of platelet-activating factor and leukotriene B4 in isolated human polymorphonuclear leukocytes

Abstract

The aim of the present work was to study interactions between the synthesis of platelet-activating factor (PAF) and leukotriene B4 (LTB4) in human polymorphonuclear leukocytes (PMNs) in vitro. PAF, at nanomolar concentrations, stimulated calcium ionophore A23187-activated PMNs to release LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE). This seems to be a receptor-mediated process as it was blocked by a PAF receptor antagonist WEB 2086 (IC50 6.6 +/- 3.9 microM). Moreover, LTB4 stimulated the formation of PAF in activated PMNs. WEB 2086 did not, however, alter PMN migration towards either LTB4 or the chemotactic peptide FMLP. This suggests that the enhancement of PAF synthesis in response to LTB4 is a concomitant event rather than a mediating process in LTB4-induced chemotactic movement of PMNs. These effects are implicated in the complex network of interactions between inflammatory mediators that results accumulation and activation of PMNs in the exacerbation of inflammatory processes.

Toll‐like receptor ligands induce polymorphonuclear leukocyte migration: key roles for leukotriene B4and platelet‐activating factor

“…LTB 4 and PAF are produced concomitantly following the activation of the group IVA phospholipase A 2 (cPLA 2 ␣) (10,11). The cPLA 2 ␣ releases arachidonic acid (AA) and lyso-PAF, the respective precursors of LTB 4 and PAF, from membrane phospholipids.…”

Leukotriene B4Induces Nitric Oxide Synthesis inTrypanosoma cruzi-Infected Murine Macrophages and Mediates Resistance to Infection

“…Here we investigated the ability of LTB 4 to induce the production of NO and whether NO mediated LTB 4 -induced parasite killing by peritoneal macrophages infected with T. cruzi in vitro. As the actions of LTB 4 may be partially dependent on the release of secondary mediators, such as PAF (13,16,18,24), we also evaluated whether LTB 4 -induced NO production and parasite killing were PAF dependent. Finally, we investigated whether endogenous production of LTB 4 played a relevant role in the infection of mice with T. cruzi in vivo.…”

Inhibition of leukotriene formation and IL-8 release by the PAF-receptor antagonist SM-12502

“…In parallel TNF-a was reported to be involved in PAF biosynthesis and vice versa, PAF also contributes to TNF-a bioactivity (31,32). Furthermore autocrine mechanisms between IL-8, LTB 4 and PAF were reported (10,11,25,33). These data provide strong evidence that distinct lipid mediators and proinflammatory cytokines establish an inflammatory network which is partially driven by autocrine mechanisms.…”

“…LTB4 at nanomolar concentrations activates several functions, such as chemotaxis, chemokinesis, aggregation, adherence to endothelium, degranulation, superoxide anion production, C3b receptor expression, complement-dependent killing, PAF synthesis, hexose uptake and oxygen consumption, and thus serves as a proinflammatory mediator in the acute phase of inflammation (25,26). LTB 4 also modulates the chronic phase of inflammation through its effects on lymphocyte functions.…”