Search

Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in [...]

We have previously demonstrated that fetal ethanol exposure deranges the function and viability of the neonatal alveolar macrophage. Although altered differentiation of the alveolar macrophage contributes to pulmonary disease states within the adult lung, the effects of fetal ethanol exposure on the normal differentiation of interstitial to alveolar macrophage in the newborn lung are unknown. In the current study, using a mouse model of fetal ethanol exposure, we hypothesized that altered terminal differentiation of the neonatal interstitial to alveolar macrophage contributes to the observed cellular dysfunction in the ethanol-exposed newborn mouse. Control alveolar macrophage differentiation was characterized by increased expression of CD32/ CDI lb (P [less than or equal to] 0.05) and increased in vitro phagocytosis of Staphylococcus aureus (P [less than or equal to] 0.05) compared with interstitial macrophage. After in utero ethanol exposure, both alveolar and interstitial macrophage lacked the acquisition of CD321CD1 lb (P [less than or equal to] 0.05) and displayed impaired in vitro phagocytosis (P [less than or equal to] 0.05). Ethanol significantly increased transforming growth factor-[[beta].sub.1] (TGF-[[beta].sub.1]) in the bronchoalveolar lavage fluid (P [less than or equal to] 0.05), as well as in both interstitial and alveolar macrophages (P [less than or equal to] 0.05). Oxidant stress contributed to the ethanol-induced changes on the interstitial and alveolar cells, since maternal supplementation with the glutathione precursor S-adenosylmethionine during ethanol ingestion normalized CD32/CD1 lb (P [less than or equal to] 0.05), phagocytosis (P [less than or equal to] 0.05), and TGF-[[beta].sub.1] in the bronchoalveolar lavage fluid and macrophages (P [less than or equal to] 0.05). Contrary to our hypothesis, fetal ethanol exposure did not solely impair interstitial to alveolar macrophage differentiation. Rather, fetal ethanol exposure impaired both neonatal interstitial and alveolar macrophage phagocytic function and differentiation. Increased oxidant stress and elevated TGF-[[beta].sub.1] contributed to the impaired differentiation of both interstitial and alveolar macrophage. alveolar macrophage; fetal alcohol; prematurity; lung doi: 10.1152/ajplung.90609.2008.

We have previously demonstrated that chronic alcohol exposure decreases glutathione in the alveolar space. Although alcohol use is associated with decreased alveolar macrophage function, the mechanism by which alcohol impairs macrophage phagocytosis is unknown. In the current study, we examined the possibility that ethanol-induced alveolar macrophage dysfunction was secondary to decreased glutathione and subsequent chronic oxidative stress in the alveolar space. After 6 wk of ethanol ingestion, oxidant stress in the alveolar macrophages was evidenced by a 30-mV oxidation of the GSH/GSSG redox potential (P [less than or equal to] 0.05). For control macrophages, ~80% internalized fluorescent Staphylococcus aureus were added in vitro. In contrast, only 20% of the macrophages from the ethanol-fed rats were able to bind and internalize fluorescent S. aureus. This ethanol-induced decreased capacity for phagocytosis was paralleled by increased apoptosis. When added to the ethanol diet, the glutathione precursors procysteine or N-acetyl cysteine normalized glutathione and oxidant stress in the epithelial lining fluid as well as the alveolar macrophages to control values. This attenuation of oxidant stress was associated with normalization of macrophage phagocytosis and viability. These results suggested that decreased glutathione availability in the alcoholic lung contribute to alveolar macrophage dysfunction via oxidative stress, resulting in not only decreased function but decreased viability. oxidative stress; apoptosis; lung; antioxidants

Intravital microscopic studies show that splanchnic artery ischemia and reperfusion (SAO/R) in rats increases the leukocyte-endothelial interaction in intestinal venules. Addition of exogenous NO donor S-nitroso-N-acetylpenicillamine (SNAP) decreases the leukocyte-endothelial interaction and plasma proteolysis. SNAP pretreatment decreases the SAO/R-induced P-selectin expression. Immunohistochemical data show that altering the leukocyte-endothelial interaction by NO proceeds through the endothelial adhesion molecule P-selectin.

The use MAb PB 1.3, a P-selectin-neutralizing monoclonal antibody, allows detection of the function of P-selectin in leukocyte-endothelium reaction following reperfusion and splanchnic arterial occlusion in pentobarbital-anesthetized rats. P-selectin is involved in accumulation of leukocytes following splanchnic ischemia-reperfusion. MAb PB1.3 reduces the polymorphonuclear leukocyte accumulation in small ischemic-reperfused bowel.

Studies on the role of a novel bradykinin receptor antagonist reveal that bradykinin is crucial in tissue injury-accompanying traumatic shock. The antagonist CP-0127 protects the tissue from the injury effects, possibly by inhibiting neutrophil-endothelial interaction and the consequent protection of vascular endothelial function.