Role for Endotoxin in the Leukocyte Infiltration Accompanying Escherichia coli Inflammation

Abstract

E. coli induce polymorphonuclear leukocyte (PMNL) infiltration during clinical (human) infection and also in a rabbit dermal model of inflammation. The factors which may mediate this host response to E. coli were investigated. In vitro incubation of Formalin-killed E. coli in heat-inactivated rabbit plasma or balanced salt solution generated in the supernatant factors which induced in vivo PMNL infiltration upon intradermal injection into rabbits. These supernatants, in the presence or absence of plasma, did not induce PMNL migration in vitro. The in vivo activity was stable at 100.degree. C and of high MW (30,000). Antiserum to O antigen or to core glycolipid, but not to K or H antigen, as well as polymyxin B inhibited the release or activity of these E. coli-derived factors. The intradermal injection of 0.02-0.2 .mu.g of 4 different endotoxin preparations or lipid A also induced marked PMNL infiltration in vivo. These preparations did not stimulate PMNL migration in vitro and failed to generate chemotactic activity in plasma except at very high concentrations (500 .mu.g/ml). Anti-O serum inhibited PMNL infiltration induced by endotoxins with the corresponding O antigen and anti-core glycolipid serum inhibited all 4 endotoxins tested; polymyxin B inhibited the activity of the endotoxins as well as that of lipid A. Base hydrolysis of endotoxin abolished PMNL infiltration. Thus endotoxin shed from E. coli (killed or live) may be 1 factor mediating the PMNL infiltration induced by this organism. Endotoxin probably acts independent of in vivo complement activation; the activity is seemingly dependent on the lipid A moiety and antibody binding to O or core glycolipid antigens may modify endotoxin so as to diminish its capacity to induce PMNL infiltration in vivo.