Circulating actin-gelsolin complexes following oleic acid-induced lung injury.
Plasma gelsolin is one of two extracellular proteins that bind actin, a major body protein, with high affinity. The authors performed a series of experiments to determine whether tissue injury leads to actin release and the formation of circulating actin-gelsolin complexes. Two functions of plasma gelsolin, filament-nucleating and filament-severing activity, were used to measure total and free gelsolin concentrations, respectively. Both gelsolin and gelsolin-actin complexes nucleate actin assembly, whereas only free gelsolin severs actin filaments. Therefore, nucleation reflects the total gelsolin concentration, severing, the free gelsolin concentration, and the difference, gelsolin-actin complexes. Injection of F-actin in the rat caused a reduction in the free, but not total, gelsolin levels, consistent with the formation of circulating actin-gelsolin complexes. Oleic acid (50 mg/kg) administered intravenously in rats, a treatment that causes acute hemorrhagic pulmonary necrosis, caused the free gelsolin concentration to fall to a greater extent than the total gelsolin concentration, which indicated the presence of circulating actin-gelsolin complexes. Lower doses (9-27 mg/kg) in rabbits caused a qualitatively similar but smaller change in the free gelsolin level. Plasma gelsolin was immunoprecipitated at times when actin-gelsolin complexes were present, as determined functionally, and bound actin was demonstrated by immunoblotting with an anti-actin antiserum. These studies show that considerable amounts of actin are released into the extracellular space during acute lung injury and that circulating actin-gelsolin complexes can be detected in the peripheral blood.
Smith
D B
DB
Hematology-Oncology Unit, Massachusetts General Hospital, Boston 02114.
Janmey
P A
PA
Lind
S E
SE
D000199:Actins / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D018260:Gelsolin; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008840:Microfilament Proteins / Q000097:blood* / Q000378:metabolism; D009829:Oleic Acids / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000199:Actins; D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; D009829:Oleic Acids