Characterization of neutrophil activation by repeated injection of endotoxin in rabbits. Role of neutrophils in the generalized Shwartzman reaction.

The relationship between activated neutrophils and end-organ injury in endotoxemia was studied. The function of peripheral blood neutrophils (PMNs) in rabbits with the generalized Shwartzman reaction (GSR) was compared to that of PMNs rabbits receiving a single injection of endotoxin. The following results were obtained: (1) PMNs from rabbits with the GSR demonstrated enhanced adherence to endothelial cells and increased mitochondrial ATP production; (2) the GSR did not enhance chemotaxis and oxygen radical production of PMNs; (3) a single injection of endotoxin did not cause necrosis of visceral organs; (4) in vitro detachment of endothelial cells by PMNs was increased in rabbits with the GSR; (5) in vivo administration of monoclonal antibody (mAb) against CD11b/CD18 (Mac-1) suppressed the increase in PMN adherence; and (6) hemorrhagic necrosis did not occur when mAb to Mac-1 was injected. Thus, enhanced adherence of PMNs to endothelial cells appears to play a key role in endotoxin-induced end-organ injuries in this animal model.