Anti-β2GPI antibodies stimulate endothelial cell microparticle release via a nonmuscle myosin II motor protein-dependent pathway

Abstract

Key Points Activation of endothelial cells by anti-β2GPI antibodies causes myosin RLC phosphorylation, leading to actin-myosin association. In response to anti-β2GPI antibodies, release of endothelial microparticles, but not E-selectin expression, requires actomyosin assembly.

AFM visualization of cortical filaments/network under cell-bound membrane vesicles

“…It is well known that cytoskeleton participates in the maintenance of membrane asymmetry and that cytoskeleton reorganization could regulate membrane budding or vesicle release [8][9][10][11]. However, previous studies generally focused on the related signal transduction pathways involved in cytoskeleton reorganization by using biochemical techniques [10,11].…”

“…However, previous studies generally focused on the related signal transduction pathways involved in cytoskeleton reorganization by using biochemical techniques [10,11]. Direct observation of the relationship between cytoskeleton and cell-bound membrane vesicles by using imaging techniques will be very important and more convincing which is currently lacking.…”

Changes in regulation of human monocyte proteins in response to IgG from patients with antiphospholipid syndrome

“…33 Of the remaining proteins we identified many of them have cytoskeletal function so it is relevant that anti-b 2 GPI antibodies mediated induction of endothelial microparticle release is dependent upon phosphorylation of the myosin regulatory light chain and assembly of actin-myosin networks. 34 Previous proteomics studies on monocytes in APS used classical proteomics techniques to identify dysregulated proteins in ex vivo monocytes from patients with APS. 10,11 López-Pedrera and colleagues identified 22 proteins that were dysregulated in monocytes of 51 patients with APS (31 with thrombosis and 19 with PM alone) compared with HC.…”

Bad (or good) things come in small packages

“…The results of this study suggest that inhibiting nonmuscle myosin II phosphorylation in endothelial cells (ECs) may block potentially deleterious microparticles from being released into the circulation. 1 …”

“…n CXCL1 excess stops neutrophils in their tracks In this issue of Blood, Yao and colleagues describe mice with vascular endothelial cell (EC) deletion of gp130, a signaling subunit for the interleukin-6 (IL-6) family of cytokines. 1 The authors postulated that such mice would exhibit an attenuated response to inflammatory stimuli but, surprisingly, the opposite phenotype was observed. These mice exhibited a dysregulated CXCL1 chemokine gradient in the endothelium, leading to neutrophils that stuck to the apical endothelial surface and were unable to exit the vessel lumen.…”