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American Journal of Pathology, Vol 139, 901-909, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Effects of all-trans retinoic acid on neutrophil-mediated endothelial cell injury in vitro and immune complex injury in rats

J Varani, J Jones, M Dame, C Sulavik, DF Gibbs and KJ Johnson
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.

All-trans retinoic acid (RA) has beneficial effects when used in a variety of inflammatory skin conditions. In this study, the authors found that RA inhibited superoxide anion production and proteolytic enzyme release by human and rat neutrophils. Concomitantly, the authors found that RA-treated neutrophils were less able than untreated neutrophils to injure endothelial cells in culture even though the adhesion of the RA-treated neutrophils to endothelial cell monolayers was not diminished. Inhibition of cytotoxicity occurred over the same range of concentrations that inhibited oxygen radical formation and protease release. In additional studies, it was observed that pretreatment of endothelial cells with RA-induced resistance to subsequent injury by activated neutrophils. Finally, in vivo studies showed that pretreatment of rats for 3 days with RA (1-10 mg/day, IP) reduced the degree of injury in the lungs and skin sites after treatment with bovine serum albumin and antibodies to bovine serum albumin in the reverse-passive Arthus reaction. Thus, RA can modulate neutrophil-mediated endothelial cell injury by an effect on both the neutrophils and their target cells. Together, these effects may underlie the reduction in immune complex-mediated injury seen in experimental animals. The beneficial effects that retinoids have in a variety of inflammatory skin diseases may likewise be a reflection of their effects on the physiology of both neutrophils and endothelial cells.

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