title: A Reservoir of Mature Cavity Macrophages that Can Rapidly Invade Visceral Organs to Affect Tissue Repair.
abstract: A key feature of inflammation is the timely recruitment of leukocytes, including monocytes, from blood into tissues, the latter maturing into macrophages over a period of 2-3 days. Using multi-channel spinning disk microscopy, we identified a rapid pathway of macrophage recruitment into an injured organ via a non-vascular route requiring no maturation from monocytes. In response to a sterile injury in liver, a reservoir of fully mature F4/80(hi)GATA6(+) peritoneal cavity macrophages rapidly invaded into afflicted tissue via direct recruitment across the mesothelium. The invasion was dependent on CD44 and DAMP molecule ATP and resulted in rapid replication and switching of macrophage toward an alternatively activated phenotype. These macrophages dismantled the nuclei of necrotic cells releasing DNA and forming a cover across the injury site. Rapid invasion of mature macrophages from body cavity with capacity for induction of reparative phenotype may impact altered tissues ranging from trauma to infections to cancer. VIDEO ABSTRACT.
authors.affiliation: Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Immunology Research Group, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Immunology Research Group, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: pkubes@ucalgary.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Kubes
mesh_terms: D000818:Animals; D002465:Cell Movement; D004195:Disease Models, Animal; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D013047:Specific Pathogen-Free Organisms; D014945:Wound Healing
chemical_list: D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse