GENERATION OF A CD11B C UP-REGULATING AND CHEMOTACTIC FACTOR BY HEPATOCYTES OF ENDOTOXIC RATS - NONIDENTITY WITH INTERLEUKIN-8/

To further clarify the mechanism of polymorphonuclear leukocyte (PMN) recruitment into the liver associated with short term endotoxin infusi on (1), we investigated the effect of a novel factor generated by hepa tocytes of such endotoxic rats on the expression of PMN adhesion molec ules CD11b/c and chemotactic activity. Conditioned medium of hepatocyt es from endotoxin-infused rats shows a fast induction and dose-depende nt activity for upregulating CD11b/c expression in and chemotactic act ivity for blood PMN of naive rats. Supernatants of naive control rats cultured in the presence of endotoxin and Kupffer cells and liver PMNs of endotoxic rats also produce activation, but to a much lesser exten t. The upregulating activity can be reduced significantly by heat inac tivation at 100 degrees C for 10 min and by pronase hydrolysis al 37 d egrees C for 60 min. Generation of the activity does not depend on cyc looxygenase products or phospholipase A2 activity, and it does not see m to be associated with the complement pathway. The activity is associ ated with molecular masses of 9-12 and 27-32 kDa and cannot be reduced by antiserum to rat interleukin-8 in serial dilutions ranging from 1: 50 to 1:25,600. The results show that hepatocytes from acutely endotox in infused rats generate a small molecular weight protein factor (or f actors) that is capable of upregulating PMN 11b/c expression and chemo tactic activity and is seemingly different from rat interleukin-8. Thu s, hepatocytes in endotoxemia may play an important role in modulating neutrophil function and contributing to the mechanism of neutrophil s equestration into the liver.