Induction of inflammatory mediators (histamine and leukotrienes) from rat peritoneal mast cells and human granulocytes by Pseudomonas aeruginosa strains from burn patients

Abstract

Clinical isolates of Pseudomonas aeruginosa from severely burned patients were analyzed with regard to their capacity to induce inflammatory-mediator release from rat mast cells or human granulocytes. The bacterial strains were characterized according to their cell-associated hemolysin activity as well as their secreted hemolysin and phospholipase C activities. P. aeruginosa expressing heat-labile hemolysin and phospholipase C induced histamine release from rat mast cells and leukotriene formation from human granulocytes, while bacterial strains expressing heat-stable hemolysin were potent releasers of histamine but did not lead to leukotriene formation. The mediator-inducing capacity was dependent on the growth characteristics of the bacterial strains. The purified glycolipid (heat-stable hemolysin) of P. aeruginosa was a potent inducer of histamine release but did not initiate leukotriene formation. Exotoxin A did not affect inflammatory-mediator release. P. aeruginosa with leukotriene-inducing capacity also enhanced omega oxidation of endogenous leukotriene B4, suggesting an additional inactivation of the chemotactic potential. Our data suggest that both hemolysins of P. aeruginosa contribute to the pathogenicity of P. aeruginosa by inducing and modulating inflammatory-mediator release from various cells.

Induction of inflammatory mediator release (serotonin and 12-hydroxyeicosatetraenoic acid) from human platelets by Pseudomonas aeruginosa glycolipid

“…Glycolipid-induced mediator release. Since, among the hemolysins, the heat-stable glycolipid has proinflammatory activities (2), experiments were carried out to analyze the effect of purified glycolipid on serotonin release and 12-HETE formation. It is evident from Fig.…”

“…Recently, we have shown that P. aeruginosa induces inflammatory mediator release from human granulocytes and mast cells in correlation to expression and secretion of the heat-labile hemolysin (phospholipase C) (2). The heat-stable hemolysin, the glycolipid, proved to be a potent stimulus for the release of the preformed mediator histamine from mast cells, but it did not induce leukotriene generation (a newly formed mediator).…”

“…Several pathogenicity factors of P. aeruginosa have been identified. Exotoxin A modulates lymphocyte functions; the heat-labile (phospholipase C) (3,4,36,40) and the heatstable (glycolipid) hemolysin (29) have been shown to induce inflammatory mediator release from human granulocytes as well as from mast cells (2). Alginate, the mucoid exopolysaccharide of P. aeruginosa which is mainly present in isolates from patients with cystic fibrosis (46), interferes with granulocyte functions, e.g., phagocytosis.…”

“…While phospholipase C induces leukotriene formation from human granulocytes, glycolipid proved to be inactive. However, glycolipid is a potent stimulus for histamine release from mast cells (2).…”

Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis

“…Leukotriene B4 (5(S), 12(R)-dihydroxyeicosa-6, \A-cis, 8,10-/ra«.5-tetraenoic acid (LTB4)) is a potent activator of neutrophils [1,2], and is produced by human macrophages and neutrophils in response to a variety of stimuli, including Pseudomonas aeruginosa [3]. The airways of patients with cystic fibrosis (CF), which are chronically colonized with Ps.…”