Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alpha IIb beta 3 activation in a Fc receptor-independent fashion.
OBJECTIVE
To characterize the activation of platelet integrin alpha IIb beta 3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4, and investigate their potential mechanism of action.


METHODS
Using 125I-labeled human fibrinogen (Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured.


RESULTS
HI117 and SJ9A4 (10 micrograms/ml and 20 micrograms/ml) induced specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alpha IIb beta 3. Further study indicated that HI117 and SJ9A4 induced integrin alpha IIb beta 3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alpha IIb beta 3 activation was inhibited by pretreatment of platelets with sphingosine, aspirin, apyrase, and/or PGI2.


CONCLUSIONS
Anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alpha IIb beta 3 activation independent of Fc-receptors. Three signaling pathways, namely thromboxane, secreted ADP, and cAMP pathways, may be involved in the process, with protein kinase C activation presumably being the common step of the three pathways.
Wu
H
H
Department of Thrombosis and Hemostasis, Department of Nuclear Medicine, Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Tianjin 300020, China. hzwu@public.tpt.tj.cn
Li
J
J
Peng
L
L
Liu
H
H
Wu
W
W
Zhou
Y
Y
Hou
Q
Q
Kong
D
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology*; D060245:Tetraspanin 29
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011961:Receptors, Fc; D060245:Tetraspanin 29; D011493:Protein Kinase C; D002118:Calcium