The immunoregulatory glycan-binding protein galectin-1 triggers human platelet activation.
Platelet activation is a critical process during inflammation, thrombosis, and cancer. Here, we show that galectin-1, an endogenous lectin with immunoregulatory properties, plays a key role in human platelet activation and function. Galectin-1 binds to human platelets in a carbohydrate-dependent manner and synergizes with ADP or thrombin to induce platelet aggregation and ATP release. Furthermore, galectin-1 induces F-actin polymerization, up-regulation of P-selectin, and GPIIIa expression; promotes shedding of microvesicles; and triggers conformational changes in GPIIb/IIIa. In addition, exposure to this lectin favors the generation of leukocyte-platelet aggregates. A further mechanistic analysis revealed the involvement of Ca(2+) and cyclic nucleotide-dependent pathways in galectin-1-mediated control of platelet activation. Finally, expression of endogenous galectin-1 in human platelets contributes to ADP-induced aggregation. Our study reveals a novel unrecognized role for galectin-1 in the control of platelet physiology with potential implications in thrombosis, inflammation, and metastasis.
Pacienza
Natalia
N
Hematological Research Institute, National Academy of Medicine, Buenos Aires, Argentina.
Pozner
Roberto G
RG
Bianco
Germán A
GA
D'Atri
Lina P
LP
Croci
Diego O
DO
Negrotto
Soledad
S
Malaver
Elisa
E
Gómez
Ricardo M
RM
Rabinovich
Gabriel A
GA
Schattner
Mirta
M
D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000502:physiology*; D005434:Flow Cytometry; D037483:Galectin 1 / Q000378:metabolism*; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D018613:Microscopy, Confocal; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000502:physiology; D015398:Signal Transduction
D000199:Actins; D037483:Galectin 1; D039661:Integrin beta3; D019007:P-Selectin; D000244:Adenosine Diphosphate