title: 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, PM(ap)). While the activation-induced microparticles have widely been studied, not much is known about the (patho)physiological consequences of PM(ap) formation. Flow cytometry and scanning electron microscopy demonstrated that PM(ap) display activated integrins and interact to form microparticle aggregates. PM(ap) were chemotactic for monocytic cells, bound to these cells, an furthermore stimulated cell adhesion and spreading on a fibronectin surface. After prolonged incubation, PM(ap) promoted cell differentiation, but inhibited proliferation. Monocyte membrane receptor analysis revealed increased expression levels of CD11b (integrin α(M)β(2)), CD14 and CD31 (platelet endothelial cell adhesion molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This indicated that PM(ap) polarized the cells into resident M2 monocytes. Cells treated with PM(ap) 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 PM(ap) 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 PM(ap) 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.
authors.affiliation: Institute for Molecular Cardiovascular Research, University Hospital Aachen, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: E M
authors.initials: EM
authors.lastname: Vasina
authors.forename: S
authors.initials: S
authors.lastname: Cauwenberghs
authors.forename: M A H
authors.initials: MA
authors.lastname: Feijge
authors.forename: J W M
authors.initials: JW
authors.lastname: Heemskerk
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: R R
authors.initials: RR
authors.lastname: Koenen
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism