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

Abstract

Key Points When activated and in platelet storage bags, platelets release respiratory-competent mitochondria, a recognized damage-associated molecular pattern. Mitochondria, descendant of Rickettsia prowazekii, serve as substrate for bactericidal sPLA2-IIA to promote inflammation.

Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer

“…3B) (7.26 ± 2.44 vs. 4.85 ± 1.46 mitochondria per platelet; P = 0.01). The absolute number of mitochondria per platelet in the control group is consistent with previous reports (17). The mitochondria from patients with cancer occupied a larger fraction of the area of the platelet (3.91 ± 1.21 vs. 2.47 ± 1.18% of platelet area; P = 0.009).…”

Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A 2 -IIA

“…Consistent with this, the blood is rich in MPs expressing platelet (and megakaryocyte) surface markers, and levels of platelet MPs increase in diseases in which platelets are activated (5). Albeit anucleated, platelets represent a major blood reservoir of such components as nuclear factors (6,7), messenger RNA (mRNA) (8,9), microRNA (miRNA) (10), and mitochondria (11), which may be packaged inside MPs and transferred to nucleated recipients. A key event in the occurrence of such transfer is the binding of platelet MPs to cells.…”

“…Whereas mitochondria are typically absent in exosomes, they can be packaged inside MPs (11,34). Furthermore, the presence of a protein associated with the endosomal sorting complex required for transport (ESCRT), tumor susceptibility gene 101 protein (TSG101), is recognized in exosomes but underrepresented in MPs (34).…”

“…Whereas sPLA 2 -IIA has limited activity on the cellular plasma membrane (27), it uses MPs as a substrate (27,29,30). Like sPLA 2 -IIA, MPs accumulate in SF during RA, where they are frequently associated with neutrophils (11,21,28,31,32).…”

“…Platelets contain an average of four mitochondria, which can be packaged inside MPs, thereby forming mitochondriacontaining MPs (11). Because only a subset of MPs contains mitochondria (11), we used confocal microscopic analyses and a combination of cytosolic and mitochondrial fluorescent dyes to distinguish mitochondria-deficient MPs and mitochondria-containing MPs.…”