CD47型
细胞生物学
流式细胞术
红细胞
细胞内
程序性细胞死亡
化学
细胞
细胞凋亡
生物
生物化学
分子生物学
作者
Rosi Bissinger,Polina Petkova-Kirova,Olga Mykhailova,Per‐Arne Oldenborg,Elena Novikova,David A. Donkor,Thomas H. Dietz,Abdulla Al Mamun Bhuyan,William P. Sheffield,Marijke Grau,Ferruh Artunç,Lars Kaestner,Jason P. Acker,Syed M. Qadri
标识
DOI:10.1186/s12964-020-00651-5
摘要
Abstract Background Thrombospondin-1 (TSP-1), a Ca 2+ -binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca 2+ dynamics, survival, and deformability of human red blood cells (RBCs). Methods Whole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca 2+ levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer. Results Exposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca 2+ levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca 2+ influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca 2+ - and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index). Conclusions Taken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca 2+ influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI