Monocyte Derived Microvesicles Deliver a Cell Death Message via Encapsulated Caspase-1

• DOI: 10.1371/journal.pone.0007140
• Publication Date: 2009-09-25T12:44:41Z
• Authors: Anasuya Sarkar; Srabani Mitra; Sonya Mehta; Raquel Raices; Mark D. Wewers
• Keywords: Transcellular; Microvesicle; Intrinsic apoptosis; Monocyte

Apoptosis depends upon the activation of intracellular caspases which are classically induced by either an intrinsic (mitochondrial based) or extrinsic (cytokine) pathway. However, in process explaining how endotoxin activated monocytes able to induce apoptosis vascular smooth muscle cells when co-cultured, we uncovered a transcellular inducing pathway that utilizes caspase-1 containing microvesicles. Endotoxin stimulated cell death VSMCs but this activity is found 100,000 g pellets free supernatants these monocytes. This not direct effect endotoxin, and inhibited inhibitor YVADcmk inhibitors Fas-L, IL-1β IL-18. Importantly, co-purifies with 100 nm sized microvesicles as determined TEM pellets. These contain encapsulation required since disruption microvesicular integrity destroys apoptotic enzymatic activity. Thus, capable delivering message release functional caspase-1. induction describes novel for inflammation programmed death.