Eierman D F, Yagami M, Erme S M, Minchey S R, Harmon P A, Pratt K J, Janoff A S
Liposome Company, Inc., Princeton, NJ 08540-6619, USA.
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2815-9. doi: 10.1073/pnas.92.7.2815.
We report that, in rats, the lethal consequences of high-dose endotoxin challenge are exacerbated by the intravascular administration of prostaglandin E1 but attenuated by the intravascular administration of endocytosable particles. This protection is mediated by opsonins. Nonopsonizable particles were unable to provide protection unless first pseudoopsonized with antibody directed against the CR3 (CD11b/CD18) phagocyte receptor. We show that endogenously opsonized particles can act in concert with prostaglandin E1 (putatively by elevation of neutrophil intracellular cAMP and the resultant downregulation of CR3) to completely rescue animals from the lethal late-stage sequelae of experimental endotoxemia. These data illustrate that the interaction of particles with cellular receptors can transform the overall systemic response to prostaglandin E1 from pro- to antiinflammatory. This suggests a role for multiple receptor engagement events in defining the systemic prostaglandin response and offers a rationale for developing new therapeutic modalities in the treatment of sepsis and other inflammatory diseases.
我们报告称，在大鼠中，高剂量内毒素攻击的致死后果会因血管内注射前列腺素E1而加剧，但会因血管内注射可内吞颗粒而减轻。这种保护作用是由调理素介导的。不可调理颗粒无法提供保护，除非先用针对CR3（CD11b/CD18）吞噬细胞受体的抗体进行假调理。我们表明，内源性调理颗粒可与前列腺素E1协同作用（可能是通过提高中性粒细胞细胞内cAMP水平以及由此导致的CR3下调），使动物完全免于实验性内毒素血症致死性晚期后遗症。这些数据表明，颗粒与细胞受体的相互作用可将对前列腺素E1的整体全身反应从促炎转变为抗炎。这表明多种受体参与事件在定义全身前列腺素反应中起作用，并为开发治疗败血症和其他炎症性疾病的新治疗方法提供了理论依据。
