title: Expression and functional implications of CCR2 expression on murine alveolar epithelial cells.
abstract: Acute lung injury results in damage to the alveolar epithelium, leading to leak of proteins into the alveolar space and impaired gas exchange. Lung function can be restored only if the epithelial layer is restored. The process of reepithelialization requires migration of lung epithelial cells to cover denuded basement membranes. The factors that control the migration of lung epithelial cells are incompletely understood. We examined isolated murine type II alveolar epithelial cells (AECs) for expression of CC chemokine receptor 2 (CCR2) and functional consequences of the binding of the main CCR2 ligand monocyte chemoattractant protein-1 (MCP-1). We found that primary AECs bound MCP-1 and expressed CCR2 mRNA. These cells demonstrated functional consequences of CCR2 expression with migration in response to MCP-1 in chemotaxis/haptotaxis assays. Primary AECs cultured from mice lacking CCR2 did not respond to MCP-1. Monolayers of AECs lacking CCR2 demonstrated delayed closure of mechanical wounds compared with AEC monolayers expressing CCR2. Delayed closure of mechanical wounds of wild-type AECs was also demonstrated in the presence of anti-MCP-1 antibody. These data demonstrate for the first time that AECs express CCR2 and are capable of using this receptor for chemotaxis and healing of wounds. CCR2-MCP-1 interactions may be important in the process of reepithelialization after lung injury.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Departmentof Internal Medicine, University of Michigan School of Medicine, and Pulmonary Section, Veterans Affairs Medical Center, Ann Arbor, 48105, USA. pchriste@umich.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christensen
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.forename: Bethany
authors.initials: B
authors.lastname: Moore
authors.forename: Susan
authors.initials: S
authors.lastname: Morris
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: Robert
authors.initials: R
authors.lastname: Paine
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology
chemical_list: C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine