title: Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice.
abstract: ARHGAP25 is a Rac-specific GTPase-activating protein that is expressed primarily in hematopoietic cells. The involvement of ARHGAP25 in regulating the recruitment of leukocytes to inflammatory sites was investigated in genetically modified mice. Using intravital microscopy, we show that Arhgap25 deficiency affects all steps of leukocyte recruitment with a predominant enhancement of transendothelial migration of neutrophilic granulocytes. Increased transmigration of Arhgap25-deficient leukocytes is demonstrated in inflamed cremaster muscle venules, in a peritonitis model, and in an in vitro chemotaxis assay. Using bone marrow chimeric mice lacking ARHGAP25 in the hematopoietic compartment, we show that enhanced migration in the absence of ARHGAP25 is due to defective leukocyte function. In search for potential mechanisms of ARHGAP25-regulated migration of neutrophils, we detected an increase in the amount of active, GTP-bound Rac and Rac-dependent cytoskeletal changes in the absence of ARHGAP25, suggesting a critical role of ARHGAP25 in counterbalancing the Rac-activating effect of nucleotide exchange factors. Taken together, using Arhgap25-deficient mice, we identified ARHGAP25 as a relevant negative regulator of leukocyte transendothelial migration.
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians Universität, 80539 Munich, Germany.
authors: Roland
authors: R
authors: Csépányi-Kömi
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and.
authors: Éva
authors: 0000-0001-8698-6867
authors: É
authors: Wisniewski
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and.
authors: Balázs
authors: B
authors: Bartos
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and.
authors: Petra
authors: P
authors: Lévai
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and.
authors: Tamás
authors: T
authors: Németh
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and.
authors: Bernadett
authors: B
authors: Balázs
authors: Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians Universität, 80539 Munich, Germany.
authors: Angela R M
authors: 0000-0002-5032-8026
authors: AR
authors: Kurz
authors: Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians Universität, 80539 Munich, Germany.
authors: Susanne
authors: S
authors: Bierschenk
authors: Walter-Brendel-Zentrum für Experimentelle Medizin, Ludwig-Maximilians Universität, 80539 Munich, Germany.
authors: Markus
authors: 0000-0002-7689-3613
authors: M
authors: Sperandio
authors: Department of Physiology, Semmelweis University, 1094 Budapest, Hungary; and ligeti.erzsebet@med.semmelweis-univ.hu.
authors: Erzsébet
authors: E
authors: Ligeti
mesh_terms: D000818:Animals; D020690:GTPase-Activating Proteins / Q000172:deficiency / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D057705:Transendothelial and Transepithelial Migration
chemical_list: C497036:ARHGAP25 protein, mouse; D020690:GTPase-Activating Proteins