Platelet dysfunction in Chediak-Higashi syndrome-affected cattle

• Published in: Journal of Veterinary Medical Science Vol. 64; no. 9; pp. 751 - 760
• Main Authors: "Shiraishi, M. (Miyazaki Univ. (Japan). Faculty of Agriculture), Ogawa, H, Ikeda, M, Kawashima, S, Ito, K.
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 01.09.2002; Japan Science and Technology Agency
• Subjects: Animals; Blood Platelet Disorders - physiopathology; Blood Platelet Disorders - veterinary; Blood Platelets - metabolism; Blood Platelets - pathology; Ca2+ signaling; CALCIUM; CATTLE; Cattle Diseases - physiopathology; Chediak-Higashi syndrome; Chediak-Higashi Syndrome - physiopathology; Chediak-Higashi Syndrome - veterinary; COLLAGEN; collagen receptor; HAEMORRHAGE; Hemorrhage - physiopathology; platelet; Platelet Aggregation; Signal Transduction
• ISSN: 0916-7250; 1347-7439
• DOI: 10.1292/jvms.64.751

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 A2, 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 alpha2beta1) 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 GPla/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. "