Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis

Stimulated mast cells release a variety of chemotactic factors such as tumo r necrosis factor alpha (TNF-alpha) and leukotriene BE. Recent studies have shown that mast cell-derived TNF-cw plays a critical role in host defense against Gram negative bacterial infections by the recruitment of neutrophil s to the sites of infection. In the present study, we sought to investigate if mast cells release leukotriene (LT) B-4. in response to bacteria and, i f so, to establish its in vivo relevance. We show that mast cells release s ignificant amounts of LTB4 and LTC4, in response to exposure to FimH-expres sing type 1 fimbriated Escherichia coli in vitro. To test the functional si gnificance of mast cell-derived LTs during an E. coil infection in vivo, we examined the effect of a LT-synthesis inhibitor, A-63162, on bacterial cle arance and neutrophil influx in an infectious peritonitis model in mast cel l-deficient mice (WBB6F(1)-W/W-v) and their normal congenic control (WBB6F( 1)-+/+) mice. Our results show that a treatment with A-63162 reduced neutro phil influx and bacterial clearance in the peritoneal cavities of mast cell -sufficient but not -deficient mice. Thus, mast cell-derived LTs contribute to host defense by mediating early neutrophil influx and bacterial clearan ce at sites of infection.