Vascular clearance and organ uptake of G- and F-actin in the rat

Abstract

This study comparatively evaluated the kinetics of removal and organ distribution of circulating G- and F-actin. Both F- and G-actin were cleared in two phases (fast component with a t1/2 of 3-5 min and a slow component with a t1/2 of hours). There was no effect of dose on either the fast- or slow-compartment clearance kinetics at the doses tested (5-100 micrograms/100 g body wt). However, at the same challenging dose of F- and G-actin, more F-actin was removed during the rapid phase. Although the time constants (Tfast) for F- and G-actin removal from the vasculature during the initial rapid phase were the same, during the slow phase the time constants (Tslow) for removal of F-actin were less (P < 0.001) than that of G-actin. The fraction of F-actin removed during the rapid phase ranged from 33 to 63% and was significantly greater (P < 0.01) than the fraction of G-actin removed during this phase (10-33%). The liver was the main organ of localization, and autoradiographic studies of liver tissue demonstrated that G-actin monomers were removed by Kupffer cells, whereas F-actin was predominantly removed by hepatic sinusoidal endothelial cells. In vivo endotoxin activation of Kupffer cells enhanced the rate of G-actin removal and increased liver localization of G-actin but had no effect on F-actin removal. This further supports a role for Kupffer cells in the clearance of G-actin. These studies therefore demonstrate that F- and G-actin clearance mechanisms are different. G-actin removal, presumably mediated by its binding to vitamin D binding protein, is accomplished by Kupffer cells, whereas F-actin removal at the same doses is due mainly to hepatic endothelial cell uptake.