Platelet dysfunction in Chediak-Higashi syndrome-affected cattle.
A serious symptom of cattle affected with Chediak-Higashi syndrome (CHS) is a bleeding tendency. This diathesis is characterized by insufficient platelet aggregation as a result of depressed response to collagen. One possible cause for the depression is a decrease in contribution of endogenous agonists such as ADP or thromboxane A(2), which are released following collagen stimulation. However, these endogenous agonists play only a minor role in collagen-induced aggregation of bovine platelets. More importantly, activation of phospholipase C as a result of a direct action of collagen is depressed, leading to a depression of Ca(2+) mobilization, in platelets from CHS-affected cattle. Several types of collagen receptor are proposed to work in concert to induce aggregation. Among them, glycoprotein VI (GPVI) and GPIa/IIa (integrin alpha2 beta1) have been supposed to play dominant roles in collagen-induced aggregation. However, there are arguments about the role of each receptor, especially the role of GPIa/IIa, and the crosstalk between receptors. Recently, we reported that the Ca(2+) signaling produced by rhodocytin, which had been first reported to be an agonist for the collagen receptor GPIa/IIa, produced much less Ca(2+) signaling in CHS platelets than in normal ones, whereas that produced by GPVI activators was normal. These suggest that GPIa/IIa or the rhodocytin-associated pathway is impaired in CHS platelets. CHS platelets are valuable to reassess the mechanism of collagen-dependent signal transduction system and to delineate the inter-relationship among collagen receptors.
Shiraishi
Mitsuya
M
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Ogawa
Hiroyuki
H
Ikeda
Masahiro
M
Kawashima
Sachiko
S
Ito
Katsuaki
K
D000818:Animals; D001791:Blood Platelet Disorders / Q000503:physiopathology* / Q000662:veterinary*; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002418:Cattle Diseases / Q000503:physiopathology*; D002609:Chediak-Higashi Syndrome / Q000503:physiopathology* / Q000662:veterinary*; D006470:Hemorrhage / Q000503:physiopathology; D010974:Platelet Aggregation; D015398:Signal Transduction