Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18).
The firm adhesion and transplatelet migration of leukocytes on vascular thrombus are both dependent on the interaction of the leukocyte integrin, Mac-1, and a heretofore unknown platelet counterreceptor. Here, we identify the platelet counterreceptor as glycoprotein (GP) Ibalpha, a component of the GP Ib-IX-V complex, the platelet von Willebrand factor (vWf) receptor. THP-1 monocytic cells and transfected cells that express Mac-1 adhered to GP Ibalpha-coated wells. Inhibition studies with monoclonal antibodies or receptor ligands showed that the interaction involves the Mac-1 I domain (homologous to the vWf A1 domain), and the GP Ibalpha leucine-rich repeat and COOH-terminal flanking regions. The specificity of the interaction was confirmed by the finding that neutrophils from wild-type mice, but not from Mac-1-deficient mice, bound to purified GP Ibalpha and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ibalpha. Finally, immobilized GP Ibalpha supported the rolling and firm adhesion of THP-1 cells under conditions of flow. These observations provide a molecular target for disrupting leukocyte-platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.
Simon
D I
DI
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. dsimon@rics.bwh.harvard.edu
Chen
Z
Z
Xu
H
H
Li
C Q
CQ
Dong
J f
Jf
McIntire
L V
LV
Ballantyne
C M
CM
Zhang
L
L
Furman
M I
MI
Berndt
M C
MC
López
J A
JA
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000502:physiology; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology*
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin