Impaired cytosolic calcium mobilization and aggregation in response to collagen in platelets from Japanese black cattle with Chediak-Higashi syndrome.
OBJECTIVE
To examine whether impaired aggregation of platelets from Japanese Black cattle with Chediak-Higashi syndrome (CHS) was attributable to mobilization of cytosolic Ca2+.


METHODS
4 healthy Japanese Black cattle and 3 Japanese Black cattle with CHS.


METHODS
Aggregation and mobilization of cytosolic Ca2+ in response to various receptor agonists was measured in platelets from healthy cattle and cattle with CHS. Involvement of endogenous ADP and arachidonic acid in collagen-induced responses was examined. Cytosolic Ca2+ concentration was measured after platelets were loaded with the Ca2+ indicator fura-PE3. Platelet aggregation was measured with an aggregometer.


RESULTS
Collagen (3 to 15 micrograms/ml)-induced increases in cytosolic Ca2+ concentration and aggregation were markedly impaired for platelets from cattle with CHS, compared with values for platelets from healthy cattle. Although aggregation and the sustained phase of the cytosolic Ca2+ response to ADP were also decreased in platelets from cattle with CHS, these decreases were small, compared with those in response to collagen. A cyclooxygenase inhibitor and a phospholipase A2 inhibitor did not have any effect on peak cytosolic Ca2+ concentration or collagen-induced aggregation of platelets from healthy cattle. Responses to a P2 tau-purinoceptor antagonist suggested that decreased release of endogenous ADP was only partially involved in the impaired response to collagen among platelets from cattle with CHS.


CONCLUSIONS
Marked inhibition of collagen-induced Ca2+ mobilization, rather than decreased release of endogenous substances, appeared to be the major cause of impaired platelet response to collagen and the hemorrhagic tendency in cattle with CHS.
Shiraishi
M
M
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Ikeda
M
M
Ogawa
H
H
Tu
C H
CH
Ito
K
K
D000244:Adenosine Diphosphate / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000097:blood*; D002609:Chediak-Higashi Syndrome / Q000097:blood / Q000662:veterinary*; D003094:Collagen / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007564:Japan; D010974:Platelet Aggregation / Q000187:drug effects*; D012016:Reference Values
D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D002118:Calcium; D007213:Indomethacin