FLow-Induced PRotrusions (FLIPRs)
- 28 February 2014
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 114 (5), 780-791
- https://doi.org/10.1161/circresaha.114.302361
Abstract
Rationale: Platelets are the most important cells in the primary prevention of blood loss after injury. In addition, platelets are at the interface between circulating leukocytes and the (sub)endothelium regulating inflammatory responses. Objective: Our aim was to study the dynamic process that leads to the formation of procoagulant and proinflammatory platelets under physiological flow. Methods and Results: In the present study, we describe the formation of extremely long, negatively charged membrane strands that emerge from platelets adhered under flow. These flow-induced protrusions (FLIPRs) are formed in vitro on different physiological substrates and are also detected in vivo in a mouse carotid injury model. FLIPRs are formed downstream the adherent and activated platelets and reach lengths of 250 μm. FLIPR formation is shear-dependent and requires cyclophilin D, calpain, and Rac1 activation. It is accompanied by a disassembly of the F-actin and microtubule organization. Monocytes and neutrophils roll over FLIPRs in a P-selectin/P-selectin glycoprotein ligand-1–dependent manner, retrieving fragments of FLIPRs as microparticles on their surface. Consequently, monocytes and neutrophils become activated, as demonstrated by increased CD11b expression and L-selectin shedding. Conclusions: The formation of long platelet membrane extensions, such as the ones presented in our flow model, may pave the way to generate an increased membrane surface for interaction with monocytes and neutrophils. Our study provides a mechanistic model for platelet membrane transfer and the generation of monocyte/neutrophil–microparticle complexes. We propose that the formation of FLIPRs in vivo contributes to the well-established proinflammatory function of platelets and platelet-derived microparticles.Keywords
This publication has 35 references indexed in Scilit:
- CRACing the ClusterCirculation Research, 2012
- Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivoThe Journal of Experimental Medicine, 2012
- Monocyte-Platelet Interaction Induces a Pro-Inflammatory Phenotype in Circulating MonocytesPLOS ONE, 2011
- Microparticles from apoptotic platelets promote resident macrophage differentiationCell Death & Disease, 2011
- Dynamics of the Rho-family small GTPases in actin regulation and motilityCell Adhesion & Migration, 2011
- Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flowBlood, 2011
- Roles of Platelet STIM1 and Orai1 in Glycoprotein VI- and Thrombin-dependent Procoagulant Activity and Thrombus FormationOnline Journal of Public Health Informatics, 2010
- Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle ProductionScience, 2010
- The calcium sensor STIM1 is an essential mediator of arterial thrombosis and ischemic brain infarctionThe Journal of Experimental Medicine, 2008
- A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion FormationThe Journal of Experimental Medicine, 2002