Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation.

TitlePlatelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation.
Publication TypeJournal Article
Year of Publication2014
AuteursBoudreau, LH, Duchez, A-C, Cloutier, N, Soulet, D, Martin, N, Bollinger, J, Paré, A, Rousseau, M, Naika, GS, Lévesque, T, Laflamme, C, Marcoux, G, Lambeau, G, Farndale, RW, Pouliot, M, Hamzeh-Cognasse, H, Cognasse, F, Garraud, O, Nigrovic, PA, Guderley, H, Lacroix, S, Thibault, L, Semple, JW, Gelb, MH, Boilard, E
JournalBlood
Volume124
Issue14
Pagination2173-83
Date Published2014 Oct 02
ISSN1528-0020
KeywordsAnimals, Blood Platelets, DNA, Mitochondrial, Endothelium, Vascular, Flow Cytometry, Group II Phospholipases A2, Humans, Inflammation, Male, Mice, Mice, Inbred C57BL, Mitochondria, Platelet Activation, Rickettsia prowazekii
Abstract

Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile nonhemolytic reactions, skin manifestations, and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospholipids, fatty acids, and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses.

DOI10.1182/blood-2014-05-573543
Alternate JournalBlood
PubMed ID25082876
PubMed Central IDPMC4260364
Grant List / / British Heart Foundation / United Kingdom
R37 HL036235 / HL / NHLBI NIH HHS / United States
R21 AR062328-01 / AR / NIAMS NIH HHS / United States
R21 AR062328 / AR / NIAMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
R01 HL036235 / HL / NHLBI NIH HHS / United States
RG/09/003/27122 / / British Heart Foundation / United Kingdom