AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 6 1071-G1081, Copyright © 1993 by American Physiological Society

ARTICLES

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

A. J. Herrmannsdoerfer, G. T. Heeb, P. J. Feustel, J. E. Estes, C. J. Keenan, F. L. Minnear, L. Selden, C. Giunta, J. R. Flor and F. A. Blumenstock
Department of Physiology and Cell Biology, Albany Medical College of Union University, Albany, New York 12208.

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.

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