Abstract

Macrophages play an important role in immune responses including allograft rejection and they are one of the potential targets of anti-rejection therapies in organ transplantation. Macrophage alloreactivity relies on their phenotype/polarity, motility, phagocytosis and matrix degradation, which in turn depend on proper functioning of actin cytoskeleton and its regulators, the small GTPase RhoA and its downstream effector the Rho-associated protein kinase (ROCK). Several laboratories showed that administration of ROCK inhibitor Y-27632 to the graft recipient inhibits chronic rejection or rodent cardiac allografts. Here we studied the effect of Y-27632 on mouse peritoneal macrophage structure, polarity and functions in in vitro assays. We show that Y-27632 inhibitor affects macrophage phenotype/polarity, phagocytosis, migration, and matrix degradation. These novel findings suggest that the impediment of macrophage structure and function via interference with the RhoA/ROCK pathway has a potential to be therapeutically effective in organ transplantation.

Original languageEnglish (US)
Pages (from-to)54-62
Number of pages9
JournalCellular Immunology
Volume300
DOIs
StatePublished - Feb 1 2016

Keywords

  • Actin
  • Macrophage
  • Matrix degradation
  • Motility
  • Phagocytosis
  • ROCK
  • RhoA
  • Y27632

ASJC Scopus subject areas

  • Immunology

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