Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury

• DOI: 10.1371/journal.pone.0145607
• Publication Date: 2015-12-28T18:41:32Z
• Authors: Srabani Mitra; Mark D. Wewers; Anasuya Sarkar
• Keywords: Proinflammatory cytokine

Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung (ALI/ARDS) impacts disease progression. has traditionally been focused on the role neutrophil trafficking to vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about pathogenesis death in ALI/ARDS, gaps remain our knowledge; as a result which there currently no effective pharmacologic therapy. Enzymes caspases are essential for completion apoptotic program secretion pro-inflammatory cytokines. We hypothesized that caspase-1 may serve key regulator human pulmonary microvascular (HPMVEC) ALI/ARDS. Our recent experiments confirm microparticles released from stimulated monocytic cells (THP1) induce apoptosis. Microparticles pretreated with inhibitor, YVAD, or pan-caspase ZVAD, were unable HPMVEC, suggesting its substrate induction HPMVEC death. Neither un-induced (control) nor direct treatment LPS HPMVEC. Further showed uptake into was facilitated interactions microparticulate vesicles. Altering vesicle integrity completely abrogated an encapsulation requirement target active caspase-1. Taken together, we microparticle centered can play injury.