Biphasic control of polymorphonuclear cell migration by Kupffer cells. Effect of exposure to metabolic products of ethanol

In order to investigate the role of the Kupffer cells in the regulation of the inflammatory reaction seen in alcoholic hepatitis, rat liver Kupffer cells were cultured and exposed to products of ethanol metabolism. The resultant supernatants were tested to study their ability to stimulate or inhibit polymorphonuclear cell chemotaxis. Kupffer cells produced increased chemokinetic activity for human polymorphonuclear leukocytes (84 +/- 6 vs. 61 +/- 4 randomly migrating cells per 5 high power fields; p less than 0.01); when incubated with soluble products of microsomal peroxidation, the Kupffer cells engendered more chemokinetic activity than that produced by untreated Kupffer cells (106 +/- 6 vs. 84 +/- 6 cells per 5 high power fields; p less than 0.05). When Kupffer cells were incubated with acetaldehyde, the chemokinetic activity that appeared in the supernatant did not differ from control (51 +/- 3 vs. 61 +/- 4 randomly migrating cells per 5 high power fields; p = NS). Chemotaxis of polymorphonuclear cells was not observed when the Kupffer cell supernatants were tested by checkerboard analysis. Kupffer cells released a factor which, at different concentrations, inhibited the response of polymorphonuclear cells to the synthetic polypeptide chemotactic factor f-met-leu-phe by 47% (p less than 0.001). This effect was unchanged when the cells were exposed to acetaldehyde or to soluble products of microsomal peroxidation. Our results demonstrate that Kupffer cells are capable of stimulating or inhibiting polymorphonuclear cell chemotaxis and that some of these effects may be influenced by the products of ethanol metabolism, suggesting that Kupffer cells may play an important role in the regulation of the inflammatory reaction seen in alcoholic hepatitis.