Microparticles from apoptotic platelets promote resident macrophage differentiation

E. M. Vasina, S. Cauwenberghs, M. A. H. Feijge, J. W. M. Heemskerk, C. Weber, R. R. Koenen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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 alpha(M)beta(2)), 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. Cell Death and Disease (2011) 2, e210; doi:10.1038/cddis.2011.94; published online 29 September 2011
Original languageEnglish
Article numbere211
Pages (from-to)10
JournalCell Death & Disease
Volume2
DOIs
Publication statusPublished - Sept 2011

Keywords

  • apoptosis
  • atherosclerosis
  • inflammation
  • platelet microparticles
  • phagocytes
  • resident macrophages

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