title: α1β1 integrin-mediated adhesion inhibits macrophage exit from a peripheral inflammatory lesion.
abstract: Integrins are adhesion molecules critical for the recruitment of leukocytes from blood into peripheral tissues. However, whether integrins are also involved in leukocyte exit from peripheral tissues via afferent lymphatics to the draining lymph node remains poorly understood. In this article, we show that adhesion by the collagen IV-binding integrin α1β1 unexpectedly inhibited macrophage exit from inflamed skin. We monitored macrophages exiting mouse footpads using a newly developed in situ pulse labeling technique. Blockade of α1β1 integrin or genetic deletion (Itga1(-/-)) increased macrophage exit efficiency. Chemotaxis assays through collagen IV showed more efficient migration of Itga1(-/-) macrophages relative to wild type. Given that macrophages are key orchestrators of inflammation, α1β1 integrin adhesion may represent a mechanism for regulating inflammatory responses by controlling macrophage exit or persistence in inflamed tissues.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada. henry.becker@utoronto.ca
authors.forename: Henry M
authors.initials: HM
authors.lastname: Becker
authors.forename: Jacob
authors.initials: J
authors.lastname: Rullo
authors.forename: Mian
authors.initials: M
authors.lastname: Chen
authors.forename: Magar
authors.initials: M
authors.lastname: Ghazarian
authors.forename: Sungho
authors.initials: S
authors.lastname: Bak
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xiao
authors.forename: John B
authors.initials: JB
authors.lastname: Hay
authors.forename: Myron I
authors.initials: MI
authors.lastname: Cybulsky
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D005528:Foot; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D039001:Integrin alpha Chains / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D039222:Integrin alpha1beta1 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D018836:Inflammation Mediators; D039001:Integrin alpha Chains; D039222:Integrin alpha1beta1; C114243:Itgb1bp1 protein, mouse; D009419:Nerve Tissue Proteins; C091367:alpha E integrins