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The Human Innunodeficiency Virus Type I Tatt Protein Potentiates Ethanol‐Induced Neutrophil Functional Impairment in Transgenic Mice
Author(s) -
Prakash Om,
Zhang Ping,
Xie Ming,
Ali Manzoor,
Zhou Peng,
Coleman Roy,
Stoltz David A.,
Bagby Gregory J.,
Shellito Judd E.,
Nelson Steve
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb05914.x
Subject(s) - integrin alpha m , genetically modified mouse , cd18 , transgene , immunology , saline , ethanol , pharmacology , phagocytosis , intraperitoneal injection , biology , flow cytometry , medicine , endocrinology , biochemistry , gene
Neutropenia and impairment of neutrophil function are commonly observed in patients with human immunodeficiency virus (HIV) infections. The HIV regulatory protein Tat is known to exert immunosuppressive effects. Alcohol is known also to be an immunosuppressive factor, and as alcohol abuse is common among HIV infected hosts, both factors may interact in an additive or synergistic fashion to further impair the host defenses of these patients. In order to test this possibility, endotoxin‐induced neutrophil β2‐integrins CD11b and CD18 expression, phagocytosis, and hydrogen, peroxide generation were examined in normal and HIV‐1 Tat‐transgenic mice in the absence and presence of ethanol intoxication. Acute ethanol intoxication was induced in mice (body weight of 25 ± 1 g) by an intraperitoneal Op) injection of ethanol (3 g/kg, 20% in normal saline). Thirty min later, the animals were given an ip injection of endotoxin (20 tig in 0.2 ml of saline/mouse). Vehicle‐treated controls received an ip injection of saline without ethanol or endotoxin. Two hr after endotoxin administration, the animals were killed to determine neutrophil functions with flow cytometry. The baseline expression of CD11b and CD18 was similar in normal nontransgenic and Tat‐transgenic mice. Endotoxin administration significantly up‐regulated CD11b and CD18 expression in normal mice. This up‐regulation was suppressed in Tat‐transgenic mice. Ethanol intoxication inhibited endotoxin‐induced CD11b and CD18 expression in normal mice and totally abolished endotoxin‐induced C011b and CD18 expression in Tat‐transgenic mice. Neutrophil phagocytic activity in normal and Tat‐transgenic mice was similar. Ethanol intoxication produced a similar inhibition of phagocytosis in both study groups. Endotoxin suppressed phagocytosis in normal mice, and this suppression was more pronounced in Tat‐transgenic mice. Spontaneous and phorbol myristate acetate (PMA)‐stimulated hydrogen peroxide generation by circulating neutrophils (PMNs) were similar in normal and Tat‐transgenic mice. Neither ethanol nor endotoxin affected hydrogen peroxide generation by PMNs. These data show that both Tat and alcohol significantly impair PMN function, and this may be a mechanism leading to the increased susceptibility of the HIV‐infected host to bacterial infection.