Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins

Lars Peter Erwig, K. A. McPhillips, M. W. Wynes, A. Ivetic, A. J. Ridley, P. M. Henson

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of apoptotic cells by macrophages or fibroblasts results in rapid phagosome maturation, whereas macrophage phagosomes containing 1g-opsonized target cells mature at a slower rate. The early maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins. Blockade of Rho signaling or inhibition of moesin both delayed maturation rates to those seen with opsonized targets. By contrast, phagosome maturation in dendritic cells was slower, similar between apoptotic and opsonized target cells, and unaffected by Rho inhibition. These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation.

Original languageEnglish
Pages (from-to)12825-12830
Number of pages5
JournalPNAS
Volume103
Issue number34
Early online date14 Aug 2006
DOIs
Publication statusPublished - 22 Aug 2006

Keywords

  • lysosomal cysteine proteases
  • apoptotic cells
  • immunological synapse
  • binding
  • phagocytosis
  • recognition
  • requirement
  • engulfment
  • clearance
  • receptors

Cite this

Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins. / Erwig, Lars Peter; McPhillips, K. A.; Wynes, M. W.; Ivetic, A.; Ridley, A. J.; Henson, P. M.

In: PNAS, Vol. 103, No. 34, 22.08.2006, p. 12825-12830.

Research output: Contribution to journalArticle

Erwig, Lars Peter ; McPhillips, K. A. ; Wynes, M. W. ; Ivetic, A. ; Ridley, A. J. ; Henson, P. M. / Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins. In: PNAS. 2006 ; Vol. 103, No. 34. pp. 12825-12830.
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AU - Wynes, M. W.

AU - Ivetic, A.

AU - Ridley, A. J.

AU - Henson, P. M.

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AB - Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of apoptotic cells by macrophages or fibroblasts results in rapid phagosome maturation, whereas macrophage phagosomes containing 1g-opsonized target cells mature at a slower rate. The early maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins. Blockade of Rho signaling or inhibition of moesin both delayed maturation rates to those seen with opsonized targets. By contrast, phagosome maturation in dendritic cells was slower, similar between apoptotic and opsonized target cells, and unaffected by Rho inhibition. These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation.

KW - lysosomal cysteine proteases

KW - apoptotic cells

KW - immunological synapse

KW - binding

KW - phagocytosis

KW - recognition

KW - requirement

KW - engulfment

KW - clearance

KW - receptors

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DO - 10.1073/pnas.0605331103

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