title: ROCK inhibition impedes macrophage polarity and functions.
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.
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
authors.forename: Yianzhu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Neelam
authors.initials: N
authors.lastname: Tejpal
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Junping
authors.initials: J
authors.lastname: You
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Xian C
authors.initials: XC
authors.lastname: Li
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA; Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston, TX, USA.
authors.forename: Rafik M
authors.initials: RM
authors.lastname: Ghobrial
authors.affiliation: The Houston Methodist Hospital Research Institute, Central South University, Changsha 410008, Hunan, China; The Department of Surgery, The Houston Methodist Hospital, Houston, TX, USA. Electronic address: mkloc@houstonmethodist.org.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kloc
mesh_terms: D064591:Allografts; D000577:Amides / Q000494:pharmacology; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006084:Graft Rejection / Q000276:immunology*; D016027:Heart Transplantation; D008262:Macrophage Activation / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D023421:Models, Animal; D011725:Pyridines / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases
keywords: Actin; Macrophage; Matrix degradation; Motility; Phagocytosis; ROCK; RhoA; Y27632