Vascular clearance and organ uptake of G- and F-actin in the rat.
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.
Herrmannsdoerfer
A J
AJ
Department of Physiology and Cell Biology, Albany Medical College of Union University, Albany, New York 12208.
Heeb
G T
GT
Feustel
P J
PJ
Estes
J E
JE
Keenan
C J
CJ
Minnear
F L
FL
Selden
L
L
Giunta
C
C
Flor
J R
JR
Blumenstock
F A
FA
D000199:Actins / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D009132:Muscles; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D000199:Actins; D007457:Iodine Radioisotopes