The role of heparin in guinea pig gram negative bacterial sepsis

The ability of antibody directed against shared antigenic determinants of gram negative organisms to protect against a challenge of diverse gram negative bacterial species remains controversial in the experimental setting. Attention has focused, however, on the use as immunogens of rough mutants of Escherichia coli and Salmonella minnesota, which express a portion of core lipopolysaccharide (LPS) extensively on their cell surface. Core LPS is a structure present on the outer membrane of most, if not all, gram negative bacteria. In this study rabbits were immunized with E. coli J5, a rough mutant of E. coli, to produce anti-E. coli J5 rabbit antiserum (anti-J5 RS). Anti-J5 RS was found to cross react extensively by enzyme-linked immunosorbent assay with various gram negative bacterial whole cell or LPS antigens, compared to normal rabbit serum (NRS). Anti-J5 RS +/- heparin was also compared to NRS +/- heparin pretreatment in a guinea pig model of sepsis utilizing E. coli O111:B4 as the challenge organism. Anti-J5 RS +/- heparin augmented systemic bacterial clearance compared to NRS +/- heparin, but only the combination of anti-J5 RS and heparin enhanced survival 48 hr after bacterial challenge. It was concluded that pretreatment with anti-J5 RS was a necessary, but not sufficient condition for enhanced survival, and that the addition of heparin to anti-J5 RS pretreatment might diminish the otherwise lethal consequences of complement activation and disseminated intravascular coagulation in this model system.