Endotoxin-induced selective dysfunction of rabbit polymorphonuclear leukocytes in response to endogenous chemotactic factors

To assess the mechanism and specificity of polymorphonuclear leukocytes (PMN) dysfunction induced by endotoxin, rabbits were injected intravenously with 100 μg of Escherichia coli endotoxin, and PMN function was studied 18 to 24 h later. Compared to PMN from normal rabbits, peripheral blood PMN from rabbits injected with endotoxin showed diminished chemotactic responsiveness to two endogenous peptides, C5a (complement) and platelet-derived growth factor, and to two endogenous lipids, leukotriene B₄ and platelet-activating factor. The chemotactic response to the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), was unimpaired. In contrast to migration, endotoxin injection resulted in inhibition of the secretory response to the two endogenous peptides but not to the lipids or to FMLP. At a 1:4 (vol/vol) dilution, the plasma either 1 or 24 h after the endotoxin injection inhibited normal PMN chemotactic responses to C5a but not to FMLP. Similarly, at a 1:10 dilution, this plasma inhibited normal PMN chemotactic responses to leukotriene B₄. The factor responsible for inhibiting responses to leukotriene B₄ was anionic, specific for leukotriene B₄ responses, and greater than 12,000 daltons. These data may be relevant to understanding PMN dysfunction during gram-negative sepsis.