Adhesion of human platelets to serum amyloid A.
Serum amyloid A (SAA) is an acute phase reactant, and its level in the blood is elevated to 1000-fold in response of the body to trauma, infection, inflammation, and neoplasia. SAA was reported to inhibit platelet aggregation and to induce adhesion of leukocytes. This study looked at adhesion of human platelets to SAA. Immobilized SAA supported the adhesion of human washed platelets; level of adhesion to SAA was comparable to fibronectin and lower than to fibrinogen. Adhesion to SAA was further enhanced by Mn(2+) and the physiological agonist, thrombin. Platelet adhesion to SAA was completely abolished by anti-SAA antibody. SAA-induced adhesion was inhibited by antibodies against the integrin receptor alphaIIbbeta3, by the peptide GRGDSP and by SAA-derived peptide containing YIGSR-like and RGD-like adhesion motifs (amino acids 29 to 42). Adhesion was not inhibited by control immunoglobulin G, by antibody against the integrin receptor alphaVbeta3, by the peptide GRGESP, and by SAA-derived peptide that includes incomplete RGD motif. SAA-derived peptide 29 to 42 also inhibited platelet adhesion to fibronectin. Transfected human melanoma cells expressing alphaIIbbeta3 adhered to SAA, whereas transfected cells expressing alphaVbeta3 did not. By using flow cytometry, the alphaIIbbeta3 cells displayed significantly higher levels of binding of soluble SAA than the alphaVbeta3 cells. These data indicate that human platelets specifically adhere to SAA in an RGD- and alphaIIbbeta3-dependent manner. Thus, SAA may play a role in modulating platelet adhesion at vascular injury sites by sharing platelet receptors with other platelet-adhesive proteins.
Urieli-Shoval
Simcha
S
Hematology Unit, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel. matzner@cc-huji.ac.il
Shubinsky
George
G
Linke
Reinhold P
RP
Fridkin
Mati
M
Tabi
Israel
I
Matzner
Yaacov
Y
D000328:Adult; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000685:Serum Amyloid A Protein; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; C047981:arginyl-glycyl-aspartic acid; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline