Angiopathic consequences of saturating the plasma scavenger system for actin.

Abstract

Two plasma proteins, vitamin D-binding protein (actin monomer sequestrant) and gelsolin (actin polymer severing), have been found in association with actin in plasma from ill humans and during experimental injury. In vitro, these are the only plasma proteins that display a high affinity for actin. We infused increasing amounts of globular actin intravenously to rats to evaluate its disposition in plasma and tissues. Intravascular filament formation, microthrombi, and endothelial injury were observed, especially in the pulmonary circulation. These pathological changes were not observed when the globular actin in the infusate had been preincubated with the vitamin D-binding protein in vitro. Complexes of actin with both proteins were found in the plasma, suggesting a saturable, plasma actin-binding system in vivo. Our findings suggest that in vivo saturation of these proteins' actin-binding capacities may serve as a paradigm for pulmonary vascular disorders seen during widespread tissue trauma and cell lysis.

Visualizing the Ca 2+ -dependent activation of gelsolin by using synchrotron footprinting

“…Gelsolin is present in both the cytoplasmic and extracellular milieus, being found in a wide range of cell types and in blood plasma (4,(11)(12)(13). The intracellular Ca 2ϩ concentration is tightly regulated in the range of 10 Ϫ7 to 10 Ϫ5 M, whereas millimolar concentrations are common in plasma.…”

Global Shapes of F-actin Depolymerization-competent Minimal Gelsolins

“…Plasma gelsolin (pGSN) is the fourth most abundant protein in human plasma and is primarily involved in the clearance of actin filaments released into the circulation upon cell necrosis (19,20). The pGSN levels decrease by 20 -50% in a wide variety of disease conditions, although a minimum threshold level of pGSN (Ն25%) is essential for maintaining the normal physiology of the body (21,22).…”

Crystal structures of the vitamin D-binding protein and its complex with actin: Structural basis of the actin-scavenger system

“…In animal experiments, rats given large amounts of actin through i.v. injection die rapidly and show evidence of pulmonary venous obstruction by actin filaments, pulmonary microthrombi, and endothelial injury (5).…”