Identification of a novel 33-kDa C1q-binding site on human blood platelets.
The constitutive expression of a 60-kDa platelet membrane protein (cC1qR) recognizing the collagen-like amino terminal of C1q was previously described. Recently, a novel 33-kDa C1q receptor (gC1qR) that interacts with the globular head region of C1q was identified on Raji cells, as well as PBLs, neutrophils, and eosinophils. The present study demonstrates that polyclonal Abs directed against this novel C1q-binding protein also recognize a 33-kDa platelet membrane constituent on Western blots. Interestingly, Ab reactivity with platelets in suspension was minimal, but increased nearly 10-fold after platelet adhesion to collagen, fibrinogen, or fibronectin-coated surfaces. Similar increases in Ab reactivity were not achieved after platelet stimulation in suspension, even with strong agonists such as thrombin or A23187. Platelet function studies, however, demonstrated that both the globular C-terminal domain of C1q and the collagen-like N-terminal region participate in platelet aggregation in response to C1q multimers. Moreover, a synthetic 18 amino acid peptide (X18) corresponding to the amino terminal sequence of the cloned Raji cell gC1qR inhibited both platelet adhesion to immobilized C1q and aggregated C1q-induced platelet aggregation. Aggregated C1q-induced platelet aggregation was also inhibited by a mAb (1B4) directed against the recombinant gC1qR. The data support the involvement of both carboxy- and amino-terminal regions of C1q in platelet-C1q interactions, and suggest a role for the gC1qR in this process.
Peerschke
E I
EI
Department of Pathology, SUNY at Stony Brook 11794.
Reid
K B
KB
Ghebrehiwet
B
B
D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins; D002462:Cell Membrane / Q000378:metabolism; D015922:Complement C1q / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000097:blood / Q000737:chemistry; D024101:Mitochondrial Proteins; D015394:Molecular Structure; D008970:Molecular Weight; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011487:Protein Conformation; D011951:Receptors, Complement / Q000378:metabolism*
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q