Varani J, Jones J, Dame M, Sulavik C, Gibbs D F, Johnson K J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Am J Pathol. 1991 Oct;139(4):901-9.
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.
全反式维甲酸（RA）用于多种炎症性皮肤病时具有有益作用。在本研究中，作者发现RA可抑制人和大鼠中性粒细胞产生超氧阴离子及释放蛋白水解酶。同时，作者发现经RA处理的中性粒细胞在培养中损伤内皮细胞的能力低于未处理的中性粒细胞，尽管经RA处理的中性粒细胞与内皮细胞单层的黏附并未减弱。细胞毒性的抑制发生在抑制氧自由基形成和蛋白酶释放的相同浓度范围内。在其他研究中，观察到用RA预处理内皮细胞可诱导其对随后活化的中性粒细胞造成的损伤产生抗性。最后，体内研究表明，用RA（1 - 10毫克/天，腹腔注射）对大鼠预处理3天，可减轻在反向被动Arthus反应中用牛血清白蛋白和抗牛血清白蛋白抗体处理后肺和皮肤部位的损伤程度。因此，RA可通过对中性粒细胞及其靶细胞的作用来调节中性粒细胞介导的内皮细胞损伤。这些作用共同可能是实验动物中免疫复合物介导损伤减少的基础。类视黄醇在多种炎症性皮肤病中具有的有益作用同样可能反映了它们对中性粒细胞和内皮细胞生理学的影响。
