Microparticles from apoptotic platelets promote resident macrophage differentiation

Abstract

Platelets shed microparticles not only upon activation, but also upon ageing by an apoptosis-like process (apoptosis-induced platelet microparticles, PMap). While the activation-induced microparticles have widely been studied, not much is known about the (patho)physiological consequences of PMap formation. Flow cytometry and scanning electron microscopy demonstrated that PMap display activated integrins and interact to form microparticle aggregates. PMap were chemotactic for monocytic cells, bound to these cells, an furthermore stimulated cell adhesion and spreading on a fibronectin surface. After prolonged incubation, PMap promoted cell differentiation, but inhibited proliferation. Monocyte membrane receptor analysis revealed increased expression levels of CD11b (integrin αMβ2), CD14 and CD31 (platelet endothelial cell adhesion molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This indicated that PMap polarized the cells into resident M2 monocytes. Cells treated with PMap actively consumed oxidized low-density lipoprotein (oxLDL), and released matrix metalloproteinases and hydrogen peroxide. Further confirmation for the differentiation towards resident professional phagocytes came from the finding that PMap stimulated the expression of the (ox)LDL receptors, CD36 and CD68, and the production of proinflammatory and immunomodulating cytokines by monocytes. In conclusion, interaction of PMap with monocytic cells has an immunomodulating potential. The apoptotic microparticles polarize the cells into a resident M2 subset, and induce differentiation to resident professional phagocytes.

Exosomes from red blood cell units bind to monocytes and induce proinflammatory cytokines, boosting T-cell responses in vitro

“…Stimulation of monocytes with apoptotic platelet EVs leads to their differentiation into resident M2 macrophages that produced proinflammatory cytokines. 43 In addition, EVs derived from LPS-stimulated monocytes or dendritic cells (DCs) activate CD4…”

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

“…[26][27][28][29][30] Microparticle-derived arachidonic acid, oxidized phospholipids, or chemokines can contribute to increased leukocyte adhesiveness. 31,32 Platelet microparticles have been shown to promote in vitro resident macrophage differentiation into professional phagocytes, 33 but the in vivo relevance of these findings is not clear and requires further study. In apolipoprotein E (ApoE) -/-mice, injection of supernatants from activated platelets (containing platelet microparticles) had no effect on leukocyte adhesion or atherosclerotic plaque size.…”

Contribution of Platelet CX 3 CR1 to Platelet–Monocyte Complex Formation and Vascular Recruitment During Hyperlipidemia

“…Blood platelets were isolated by centrifugation of platelet-rich plasma samples 28,29 from healthy volunteers after informed consent and approval of the Ethical Committees in Aachen and Munich (Germany). Monocytes were prepared from human or mouse peripheral blood mononuclear cells by negative selection with MACS isolation kit (Miltenyi Biotec, Bergisch Gladbach, Germany).…”

“…29,31 For detection of PMC by FACS, antimouse CD41-PE, CD11b-PerCP5.5, and CD45-APC-Cy7 antibodies were used.…”