Inhibition of collagen-induced platelet aggregation in Japanese black cattle with inherited platelet disorder, Chediak-Higashi syndrome.
Aggregation properties of platelets were examined in Japanese Black cattle with Chediak-Higashi syndrome (CHS) and normal control cattle. Platelet aggregation induced by collagen was decreased in platelets of the cattle with CHS, but not ADP (10-20 microM), thrombin (0.5-1.0 U/ml) and phorbol-12-myristate 13-acetate (PMA, 3.2 microM). The aggregation response induced by collagen in CHS platelets lacks the change in shape which usually occurs in normal platelets. Simultaneous stimulation by collagen (10 micrograms/ml) + ADP (10 microM) is effective in restoring collagen-induced aggregating response in CHS platelet, although pretreatment of ADP (10 microM) could not restore the collagen (10 micrograms/ml)-induced aggregating response, suggesting that there is a certain threshold of stimulation intensity above which collagen-induced aggregation of CHS platelet can begin. Control normal platelets, previously exposed to ADP (10 microM) and collagen (10 micrograms/ml), showed no further response to exposure to a third aggregating agent (arachidonic acid, 5 mM). On the other hand, the final agent was able to elicit aggregating responses in CHS platelets, suggesting that the arachidonate aggregating system may be suppressed in CHS cattle, but fully activated in control animals. Furthermore, normal platelets showed a significant decrease in aggregating response to collagen when pretreated with a cyclooxygenase inhibitor, indomethacin (10(-5) M), whereas CHS platelet was insensitive to indomethacin. This indomethacin-treated normal platelet mimicked the CHS collagen-induced aggregation pattern. These data suggest that a signal transduction process from receptor-operated events to arachidonate metabolism is suppressed in collagen-induced CHS platelet aggregation.
Suzuki
T
T
Department of Veterinary Pharmacology, Faculty of Agriculture, Iwate University, Ueda, Japan.
Goryo
M
M
Inanami
O
O
Uetsuki
J
J
Saito
S
S
Kaketa
K
K
Oshima
T
T
Shimizu
H
H
Okabe
S
S
Tanaka
T
T
Kamata
R
R
Shuto
F
F
Sato
I
I
Tachikawa
E
E
Sakaguchi
M
M
Kobayashi
H
H
Okada
K
K
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases; D002609:Chediak-Higashi Syndrome / Q000097:blood / Q000235:genetics / Q000662:veterinary*; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin