Gender differences in nitric oxide production by alveolar macrophages in ethanol plus lipopolysaccharide-treated rats.
Alveolar macrophages (AMs) constitute an important first line of host defense against infection in the lung, and NO is an essential component of the microbicidal activity of cytokine-activated macrophages. Previously we studied the respiratory burst, protein kinase C activity, and NO generation in tumor necrosis factor (TNF) and lipopolysaccharide (LPS)-treated AMs and gender differences in phagocytosis in ethanol (EtOH)-intoxicated rats. Now we have investigated NO production by AMs in EtOH plus LPS-treated male and female rats. Rats were infused iv with EtOH for 3 h to a blood level of approximately 180 mg/dl. At 90 min of infusion, Escherichia coli LPS (750 microg/kg) was injected i.v. Controls received saline (SAL) + LPS. AMs were isolated by bronchoalveolar lavage and cultured for 20 h in the absence and presence of LPS, interferon-y (IFN), and LPS + IFN. Nitrite was determined in the medium and was taken as an index of NO production. EtOH alone resulted in no significant differences compared with SAL infusion. LPS treatment caused a decrease in basal and an increase in LPS and IFN-stimulated generation of NO in males and females. EtOH + LPS treatment vs EtOH showed no significant differences. There are gender differences in both spontaneous and in vitro stimulated NO production by AMs. AMs of female rats treated with SAL + LPS released significantly more NO spontaneously than AMs of equally treated male rats. Cells of SAL + LPS-treated male rats activated in vitro by LPS and IFN-gamma produced significantly greater amounts of NO than AMs of female rats. These differences in activated induction of NO production were abrogated by ethanol treatment.
Department of Physiology and Alcohol Research Center, Louisiana State University Medical Center, New Orleans 70119, USA.
J A
JA
Spitzer
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D000431:Ethanol; D007371:Interferon-gamma