Affiliation:
1. From the Department of Laboratory Medicine, Children's Hospital Boston, and the Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Abstract
It has recently been shown that the Gardos channel activity of mouse erythrocytes can be modified by endothelins, suggesting a functional linkage between endothelin receptors and the Gardos channel. Using 86Rubidium (86Rb) influx, effects were estimated of proinflammatory molecules such as platelet activator factor (PAF), endothelin-1 (ET-1), interleukin-10 (IL-10), and regulated on activation normal T cells expressed and secreted (RANTES) on the Gardos channel activity in human normal and sickle red cells. It was found that PAF (EC50: 15 ± 7 nM), RANTES (EC50, 9 ± 6 ng/mL [1.2 ± 0.8 nM]), IL-10 (EC50, 11 ± 8 ng/mL [204 ± 148 nM]), and ET-1 (EC50, 123 ± 34 nM) induce a significant increase in Gardos channel activity—between 28% and 84%—over the control. In addition, these agents modify the Gardos channel affinity for internal Ca++ (K0.5) by 2- to 6-fold. Biochemical evidence is provided for the presence of ET receptor subtype B in sickle and normal red cells. Furthermore, it was found that ET-1, PAF, RANTES, and IL-10 induce a significant increase in red cell density (P < .05). These data suggest that activation of the Gardos channel is functionally coupled to receptor motifs such as C-X-C (PAF), C-C (RANTES), and ET receptor subtype B. Thus, cell volume regulation or erythrocyte hydration states might be altered by activation of the Gardos channel by cytokines in vivo. The role of these mediators in promoting sickle cell dehydration in vivo is under investigation.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
75 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献