Antithrombin III reduces collagen-stimulated granule secretion of PDGF-AB and the release of soluble CD40 ligand from human platelets.
Although antithrombin-III (AT-III), an anti-coagulant, has been shown to affect human platelet functions, the direct effect of AT-III on platelets is still unknown. We recently reported that the collagen-induced phosphorylation of the heat shock protein 27 (HSP27) via the p44/p42 mitogen-activated protein (MAP) kinase is sufficient for granule secretion and the release of soluble CD40 ligand (sCD40L) from platelets but not platelet aggregation. In the present study, we investigated whether AT-III affects the collagen-induced secretion of the platelet-derived growth factor (PDGF)-AB and sCD40L release. AT-III inhibited collagen-stimulated platelet aggregation. The collagen-induced secretion of PDGF-AB was significantly suppressed by AT-III. AT-III also reduced sCD40L release. AT-III markedly attenuated the collagen-induced phosphorylated levels of p44/p42 MAP kinase. In addition, AT-III suppressed collagen-induced HSP27 phosphorylation. These results strongly suggest that AT-III reduced collagen-stimulated platelet granule secretion due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase.
Doi
Tomoaki
T
Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Adachi
Seiji
S
Matsushima-Nishiwaki
Rie
R
Kato
Hisaaki
H
Enomoto
Yukiko
Y
Natsume
Hideo
H
Kato
Kenji
K
Mizutani
Jun
J
Otsuka
Takanobu
T
Tokuda
Haruhiko
H
Akamatsu
Shigeru
S
Iwama
Toru
T
Kozawa
Osamu
O
Ogura
Shinji
S
D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000494:pharmacology* / Q000502:physiology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*
D000925:Anticoagulants; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D023201:CD40 Ligand; D000990:Antithrombin III; D003094:Collagen