title: Ethanol suppresses phagosomal adhesion maturation, Rac activation, and subsequent actin polymerization during FcγR-mediated phagocytosis.
abstract: Clinical and laboratory investigations have provided evidence that ethanol suppresses normal lung immunity. Our initial studies revealed that acute ethanol exposure results in transient suppression of phagocytosis of Pseudomonas aeruginosa by macrophages as early as 3 h after initial exposure. Focusing on mechanisms by which ethanol decreases macrophage Fcγ-receptor (FcγR) phagocytosis we targeted the study on the focal adhesion and cytoskeletal elements that are necessary for phagosome progression. Ethanol inhibited macrophage phagocytosis of IgG-coated bead recruitment of actin to the site of the phagosome, dampened the phosphorylation of vinculin, but had no effect on paxillin phosphorylation suggesting a loss in "phagosomal adhesion" maturation. Moreover, our observations revealed that FcγR-phagocytosis induced Rac activation, which was increased by only 50% in ethanol exposed cells, compared to 175% in the absence of ethanol. This work is the first to show evidence of the cellular mechanisms involved in the ethanol-induced suppression of FcγR-mediated phagocytosis.
authors.affiliation: Program of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL, United States.
authors.forename: John
authors.initials: J
authors.lastname: Karavitis
authors.forename: Eva L
authors.initials: EL
authors.lastname: Murdoch
authors.forename: Cory
authors.initials: C
authors.lastname: Deburghgraeve
authors.forename: Luis
authors.initials: L
authors.lastname: Ramirez
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D022001:Focal Adhesions / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051419:Paxillin / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D058105:Polymerization; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D016596:Vinculin / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D051419:Paxillin; D017452:Receptors, IgG; D016596:Vinculin; D000431:Ethanol; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins