ABSENCE OF A DEMONSTRABLE EFFECT FOR ENDOTOXIN ON THE LYSOSOMAL ENZYME ACTIVITY OF RECRUITED MACROPHAGES IN A RAT MODEL OF LIVER INJURY

Abstract

The endotoxin dose response of recruited and activated tissue macrophages isolated from a rat model of liver injury has been measured after 24 hours in in vitro culture, with respect to their production of a lysosomal enzyme, N-acetyl-glucosaminidase (tlAG). There were no significant differences in the NAG activity in cell lysates or supernatants following a two-hour exposure of the macrophages to a range of endotoxin concentrations (50 ~g. 5 ng./rnl.); nor were any significant differences observed when compared to NAG activity of cells recruited but not exposed to endotoxin. The level of NAG activity in the supernatants and cell lysates of these recruited cells was significantly higher (p<:O.02) than the levels measured in resident macrophages (Kup7.fer cells)isolated from normal rat livers. We conclude that with respect to lysosomal enzyme release these cells have already been maximal.ly activated in vivo and that further hepatic daQage induced by endotoxin .:l.uministration occurs through mechanisms other than increased release of lysosomal enzymes.