Modulation of leukotriene generation by invasive bacteria.

The effect of invasive bacteria on the release of proinflammatory mediators (oxygen radicals, leukotriene release) from human polymorphonuclear neutrophils was studied. Bacterial stimuli were used including genetically cloned invasive Yersinia enterocolitica strains 108-P (bearing the phagocytosis-resistance plasmid) and 108-C (plasmidless variant), Listeria monocytogenes [SLCC 5779 (inv-) and NCTC 7973 (inv+)] as well as an Escherichia coli K 12 strain (pRI 203) in which the inv gene of Y. pseudotuberculosis was cloned. When human polymorphonuclear granulocytes were studied as target cells the inv+ as well as the inv- strains were phagocytosed to a comparable amount with the exception of the L. monocytogenes strain (inv+). Among the invasive strains E. coli HB 101 (pRI 203) was the most active to trigger polymorphonuclear leucocytes (PMN) for oxygen radical production. Preincubation of the cells with bacteria and subsequent stimulation with the Ca ionophore A23187 or opsonized zymosan suppressed the chemiluminescence response to a different degree. The various bacterial strains did not induce leukotriene release from endogenous arachidonic acid. Subsequent stimulation of the infected cells with Ca ionophore or opsonized zymosan led to an altered pattern of the combined amounts of leukotriene B4 (LTB4), 20-OH- and 20-COOH-LTB4 as well as the ratio of LTB4 versus 20-OH and 20-COOH-LTB4. Infection of the cells also reduced strain dependently the number of LTB4-receptor sites. Our data suggest that bacterial uptake modulates the inflammatory response of granulocytes (e.g. chemiluminescence response, leukotriene generation).