Effect of ethanol on functions required for the delivery of neutrophils to sites of inflammation.
Acute ethanol intoxication inhibits neutrophil delivery to sites of inflammation and, concomitantly, reduces the adhesion of neutrophils to surfaces. The effect of ethanol on several other neutrophil functions required for normal delivery are examined herein. Serum-free neutrophil suspensions showed normal resting adherence to endothelial monolayers in ethanol concentrations up to 1000 mg/dL, but when neutrophils were stimulated by 10(-6)M N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to induce hyperadherence, ethanol induced a dose-dependent inhibition that was significant at concentrations greater than or equal to 500 mg/dL. Pretreating the endothelium with ethanol had no effect. Similarly, resting surface expression of the adhesive glycoprotein Mac-1 was unaffected by ethanol, but its up-regulation induced by fMLP was inhibited by 25.5% at 250 mg of ethanol/dL and by 52.3% at 1000 mg/dL. Release of both primary and secondary granule contents after activation showed dose-dependent inhibition, whereas resting granule content and spontaneous release were unaffected. Passive neutrophil deformability was significantly enhanced in 500 mg of ethanol/dL. Thus, ethanol affects several neutrophil delivery functions normally activated by inflammatory stimuli.
MacGregor
R R
RR
Infectious Diseases Section, University of Pennsylvania School of Medicine, Philadelphia.
Safford
M
M
Shalit
M
M
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000502:physiology; D004727:Endothelium / Q000166:cytology; D000431:Ethanol / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D016169:Lymphocyte Function-Associated Antigen-1; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D014155:Transcobalamins / Q000378:metabolism
D000954:Antigens, Surface; D016169:Lymphocyte Function-Associated Antigen-1; D014155:Transcobalamins; D000431:Ethanol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005966:Glucuronidase