Functional role of antibody against "core" glycolipid of Enterobacteriaceae.
Antibodies against the "core" glycolipid of Enterobacteriaceae (2-keto, 3-deoxyoctonate-Lipid A) have been associated with protection against the sequelae of gram-negative rod bacteremia. To investigate the nature of this protection, dogs and rabbits were immunized with purified glycolipid prepared by phenol-chloroform-petroleum ether extraction of the "Re" mutant of Salmonella minnesota 595 and opsonophagocytic and bactericidal tests were carried out using lapine peritoneal granulocytes and serum factors. Whereas 1-4 mug/kg of glycolipid i.v. produced hypotension in dogs and 8 mug/kg i.v. was lethal, a rising dosage schedule of immunization with an average total dose of 1 mg/kg produced striking protection against shock and death against challenge with heterologous organisms. 20 control dogs, given approximately 10(10) live, serum-resistant Escherichia coli 0.85:H9 or Serratia marcescens 03 during a continuous intra-arterial pressure transducer recording, showed a drop in mean systolic pressure from 186 (+/- 6 SE) to 101 (+/- 12 SE) MM Hg and a fall in mean diastolic pressure from 118 (+/- 3 SE) to 64 (+/- 8 SE) mm Hg within 60-120 min. Minor pressure changes (average less than 12% of prechallenge levels) were seen in the same number of immunized dogs. In contrast, no significant difference was noted in the bloodstream clearance of these serum-resistant organisms over a period of 4-6 h between immunized and control dogs. Intravascular clearance was greater in animals immunized with the challenged strain or in glycolipid-immunized animals challenged with highly serum-sensitive E. coli 0.14:K7. Antibody against core glycolipid protected against the hemodynamic sequelae of bacillemia, augmented intravascular clearance of serum-sensitive organisms, and abrogated the pyrogenic response to enteric bacilli, but did not enhance clearance of serum-resistant organisms. Although canine and lapine antiserum against core glycolipid passively protected mice against a heterologous challenge, opsonophagocytic and bactericidal activity was at least 100-fold less than type-specific antiserum.
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000918:Antibody Specificity; D000992:Antitoxins; D001770:Blood Bactericidal Activity; D001794:Blood Pressure; D001831:Body Temperature; D003429:Cross Reactions; D004285:Dogs; D004755:Enterobacteriaceae / Q000276:immunology*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000517:prevention & control; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D006017:Glycolipids / Q000276:immunology*; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D009895:Opsonin Proteins; D010587:Phagocytosis; D011817:Rabbits; D012475:Salmonella / Q000276:immunology*; D012706:Serratia marcescens / Q000276:immunology*
D000907:Antibodies, Bacterial; D000992:Antitoxins; D006017:Glycolipids; D009895:Opsonin Proteins