Abstract
Microparticles (MPs) are small membrane fragments shed from normal as well as activated, apoptotic or injured cells. Emerging evidence implicates MPs as a causal and/or contributing factor in altering normal vascular cell phenotype through initiation of proinflammatory signal transduction events and paracrine delivery of proteins, mRNA and miRNA. However, little is known regarding the mechanism by which MPs influence these events. Caveolae are important membrane microdomains that function as centers of signal transduction and endocytosis. Here, we tested the concept that the MP-induced pro-inflammatory phenotype shift in endothelial cells (ECs) depends on caveolae. Consistent with previous reports, MP challenge activated ECs as evidenced by upregulation of intracellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 upregulation was mediated by activation of NF-κB, Poly [ADP-ribose] polymerase 1 (PARP-1) and the epidermal growth factor receptor (EGFR). This response was absent in ECs lacking caveolin-1/caveolae. To test whether caveolae-mediated endocytosis, a dynamin-2 dependent process, is a feature of the proinflammatory response, EC’s were pretreated with the dynamin-2 inhibitor dynasore. Similar to observations in cells lacking caveolin-1, inhibition of endocytosis significantly attenuated MPs effects including, EGFR phosphorylation, activation of NF-κB and upregulation of ICAM-1 expression. Thus, our results indicate that caveolae play a role in mediating the pro-inflammatory signaling pathways which lead to EC activation in response to MPs.
Highlights
Microparticles (MPs) are small 0.1 to 1.0 μm membrane fragments shed from activated, apoptotic or injured cells
Given the role of caveolae as signaling microdomains in the endothelium, we tested whether caveolae organelles participated in MP-induced signaling pathways that govern adhesion molecule expression
To determine the involvement of caveolae endocytosis in MP-induced signaling we examined the effect of dynasore on p65 and epidermal growth factor receptor (EGFR) phosphorylation
Summary
Microparticles (MPs) are small 0.1 to 1.0 μm membrane fragments shed from activated, apoptotic or injured cells. Microparticles Activate the Endothelium via Cav-1 primarily shed from endothelial cells, platelets and immune cells [2] and carry proteins, mRNA and miRNA [3]. They can interact and/or be taken up in other cells and affect signaling, protein expression and cellular phenotype [4, 5]. Recent evidence suggests that MPs can play a role in inflammation [6, 7], thrombosis [8], coagulation [9], impair vasorelaxation [10] and induce oxidative stress [7, 11] contributing to disease progression
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.