Angiopathic consequences of saturating the plasma scavenger system for actin.
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.
Haddad
J G
JG
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
Harper
K D
KD
Guoth
M
M
Pietra
G G
GG
Sanger
J W
JW
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000097:blood / Q000302:isolation & purification; D004797:Enzyme-Linked Immunosorbent Assay; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018260:Gelsolin; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism; D008840:Microfilament Proteins / Q000097:blood / Q000302:isolation & purification; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013861:Thiocyanates; D014809:Vitamin D-Binding Protein / Q000097:blood* / Q000302:isolation & purification
D000199:Actins; D002135:Calcium-Binding Proteins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018260:Gelsolin; D008840:Microfilament Proteins; D013861:Thiocyanates; D014809:Vitamin D-Binding Protein; D016650:Fluorescein-5-isothiocyanate