IMPAIRED SUPEROXIDE ANION, PLATELET-ACTIVATING-FACTOR, AND LEUKOTRIENE B4 SYNTHESIS BY NEUTROPHILS IN CIRRHOSIS

Background: Several alterations of polymorphonuclear leukocyte (PMN) function were found in alcoholic cirrhotics that may contribute to augmented susceptibility to infections. We evaluated function and synthesis of lipid mediators in PMN obtained from nonalcoholic cirrhotics. Methods: We evaluated the phagocytic and chemotactic response together with superoxide anion (O2-), leukotriene B4, (LTB4 and platelet-activating factor (PAF) production in response to different stimuli in PMN from nonalcoholic cirrhotics as compared with controls. Results: PMN from cirrhotics showed, after stimulation with opsonized zymosan (STZ) and phorbol-12-myristate-13-acetate, a reduced capacity to produce O2- when compared with controls. [3H]acetate incorporation into PAF was significantly higher in PMN obtained from controls in respect to cirrhotics. Gas chromatography/mass spectrometry analysis confirmed a reduced PAF synthesis by PMN obtained from cirrhotics. LTB4 production from PMN, after stimulation with calcium ionophore (A23187) and STZ, was significantly reduced in cirrhotics. [3H]arachidonic acid release from prelabeled PMN, measured upon stimulation with A23187 and STZ, was higher in controls than in cirrhotics. Conclusions: An altered synthesis of LTB4 and PAF is associated with an impaired O2- production by PMN in nonalcoholic cirrhosis. Reduced synthesis of lipid mediators may be related to an altered phospholipase A, activity. © 1993.