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.