Acute Ethanol Intoxication Inhibits Neutrophil β2-Integrin Expression in Rats During Endotoxemia

Authors

  • Ping Zhang,

    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • Gregory J. Bagby,

    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • Ming Xie,

    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • David A. Stoltz,

    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • Warren R. Summer,

    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • Steve Nelson

    Corresponding author
    1. Department of Medicine-Section of Pulmonary and Critical Care Medicine (P.Z., W.R.S., S.N.), Department of Physiology (G.J.B., D.A.S.), and the Alcohol Research Center (P.Z., G.J.B., D.A.S., W.R.S., S.N.), Louisiana State University Medical Center, New Orleans, Louisiana; and the Department of Pathology (M.X.), University of Chicago Hospital, Chicago, Illinois.
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  • This study was supported by the National Institutes of Health Grant AA-09803.

Reprint requests: Steve Nelson, M.D., Department of Medicine-Section of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, 1901 Perdido Street, New Orleans, LA 70112.

Abstract

The effects of acute ethanol intoxication on neutrophil [polymorphonuclear leukocyte (PMN)] adhesion molecule expression and certain other functional properties during endotoxemia were studied in rats to elucidate the mechanisms underlying the immunosuppressive effects of ethanol. Acute ethanol intoxication was induced by an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of ethanol/kg. Control animals received an intraperitoneal injection of saline. Thirty minutes after intraperitoneal injection, animals were given a 90-min intravenous infusion of Escherichia coli endotoxin (total dose of 112.5 μg/rat in 2.5 ml of saline) or saline. Certain rats received granulocyte colony-stimulating factor (G-CSF; 50 μg/kg in 5% dextrose, subcutaneous injection twice daily) or vehicle pretreatment for 2 days before intravenous endotoxin infusion. Endotoxemia significantly upregulated CD11b/c and CD18 expression on PMNs when compared with those of saline-infused rats. Acute ethanol intoxication inhibited this endotoxin-induced upregulation of CD11b/c and CD18 expression on PMNs. Ethanol intoxication also suppressed the phagocytic activities of PMNs in saline-infused rats, but this suppression failed to reach statistical significance in endotoxin-infused rats. Hydrogen peroxide generation by PMNs in saline- or endotoxin-infused rats was not affected by ethanol intoxication. Histological examination showed extensive PMN sequestration in the liver after endotoxin infusion, and ethanol intoxication significantly attenuated this hepatic sequestration of PMNs. G-CSF pretreatment enhanced neutrophil phagocytosis, CD11b/c and CD18 expression in endotoxin-infused rats, and prevented the ethanol-induced inhibition of neutrophil CD18 expression and phagocytosis. The impairment of β2-integrin expression on PMNs may be one mechanism underlying ethanol-induced defects of neutrophil delivery into tissue sites of infection. G-CSF may be of benefit to the infected alcoholic host by enhancing leukocyte defense functions.

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