Chronic alcoholics are most susceptible to infections and have increased incidences of certain types of carcinomas. One explanation for this may be suppressed immune responses secondary to ethanol intake. Because granulocytes are the major components of the host defense mechanism against infections, and because ethanol ingestion may directly inhibit the proliferation of neutrophil progenitor cells, studying the effect of ethanol on granulocyte differentiation using an established HL-60 cell culture model system may give a better understanding of the pathogenesis of decreased host resistance to infections in alcoholics. Our goals are to: (i) determine the effect of ethanol on DMSO-induced granulocyte differentiation; (ii) determine changes in cellular NAD+ content in HL-60 cells exposed to DMSO, ethanol and their combination; (iii) measure changes in NAD+ glycohydrolase activity; and (iv) measure changes in poly(ADP-ribose) synthetase activity. These specific goals are designed to test the hypothesis that: ethanol inhibits granulopisis by altering cellular NAD+ metabolism.
