Alterations in endothelial barrier permeability in multiple organs during overactivation of macrophages in rats

Macrophage hyperactivity has been suggested to play an important role in septic complications and the development of multiple organ failure. Intraperitoneal administration of macrophage stimulants, e.g., zymosan, induce a systemic inflammatory response, with concomitant gut origin sepsis, and organ dysfunction. However, little is known about alterations in endothelial permeability during macrophage hyperactivation. In the present study, the effect of macrophage hyperactivation on endothelial permeability, assessed by 125I-labeled HSA and 51Cr-labeled EDTA, and the difference between cytolytic and noncytolytic inflammatory macrophages induced by i.p. injection of .25 or .50 mg/g of zymosan, concanavalin A (Con A) or thioglycollate medium (TM) diluted in 4 mL of paraffin, as well as the potential relationship with the doses used, were evaluated in the rat. Overactivation of cytolytic inflammatory macrophages induced a pronounced alteration in endothelial barrier permeability, characterized by a decrease in whole body plasma volume and an increase in whole body interstitial fluid volume, while overactivation of noncytolytic inflammatory macrophages only induced leakage of proteins and plasma to several of the organs studied. Macrophage activators, like zymosan, Con A and TM, exhibited varying effects on endothelial permeability related to the dose used. The results in the present study imply that overactivation of cytolytic inflammatory macrophages may play an important role in endothelial barrier injury and that zymosan possesses a more potent effect as compared to Con A when administered at the same dose.