A novel anti-platelet monoclonal antibody induces mouse platelet aggregation through an Fc receptor-independent mechanism.
Platelets are nonproliferative and terminally differentiated cells. Platelets offer an attractive model system to study the various biochemical events leading to structural and functional alterations in activated cells. When platelets are exposed to stimuli, they are activated, undergo a dramatic shape change, adhere to each other, and aggregate. Several monoclonal antibodies (mAbs) that recognize CD9, GPIIb/IIIa (alpha IIb beta 3 intergrins), or GPIV are known to stimulate human platelet aggregation. However, no mAbs able to induce aggregation of mouse platelets have been reported. We have established an anti-mouse platelet mAb (AIP21) that can promote mouse platelet aggregation by itself. Because mouse platelets did not express the Fc receptor (FcR, CD32) on their surfaces and because AIP21 is an IgM subclass, AIP21 might promote platelet aggregation through an FcR-independent mechanism. We could not identify the antigen recognized by AIP21, but flow cytometric analysis revealed that it was not identical to CD9, GPIV, or integrins (i.e., alpha IIb, alpha v, alpha 5, alpha 6, beta 1, and beta 3 integrins). During the aggregation of mouse platelets mediated by AIP21, several 50-68-kDa proteins are rapidly phosphorylated at tyrosine residues. This phosphorylation by AIP21 was dose-dependent and did not require plasma components. We identified the 52-kDa phosphorylated protein as Shc. These results indicate that AIP21 could be useful for investigating the mechanisms of mouse platelet aggregation.
Kato
Y
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Hori
S
S
Fujita
N
N
Tsuruo
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D015539:Platelet Activation / Q000276:immunology; D010974:Platelet Aggregation / Q000276:immunology*; D011233:Precipitin Tests; D011961:Receptors, Fc / Q000032:analysis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D011961:Receptors, Fc; D019000:Phosphotyrosine