Anti-human platelet tetraspanin (CD9) monoclonal antibodies induce platelet integrin alphaIIbbeta3 activation in a Fc receptor-independent fashion.
OBJECTIVE
This study characterized the activation of platelet integrin alphaIIbbeta3 induced by two anti-human platelet tetraspanin monoclonal antibodies (mAbs), HI117 and SJ9A4.


METHODS
Using 125I-labeled human fibrinogen(Fg), specific Fg binding to human platelets induced by HI117 and SJ9A4 was measured as indication of activation of platelet integrin alphaIIbbeta3 by the two mAbs.


RESULTS
HI117 and SJ9A4 (10 microg/ml and 20 microg/ml) induced evident specific Fg binding to human platelets, suggesting that the two mAbs evoked activation of platelet integrin alphaIIbbeta3. Further study indicated that HI117 and SJ9A4 induced integrin alphaIIbbeta3 activation independent of platelet Fc-receptors, and that HI117 and SJ9A4-induced integrin alphaIIbbeta3 activation was inhibited by sphingosing, aspirin, apyrase, and/or PGI2.


CONCLUSIONS
The anti-platelet tetraspanin (CD9) mAbs, HI117 and SJ9A4, can induce platelet integrin alphaIIbbeta3 activation independent of Fc-receptor. Three signaling pathways, i.e. 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
Institute of Hematology, CAMS & PUMC, Tianjin 300020.
Li
J
J
Peng
L
L
Liu
H
H
Wu
W
W
Zhou
Y
Y
Hou
Q
Q
Ke
D
D
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; 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