title: Lung pericyte-like cells are functional interstitial immune sentinel cells.
abstract: Pericytes are perivascular PDGF receptor-β+(PDGFRβ+) stromal cells required for vasculogenesis and maintenance of microvascular homeostasis in many organs. Because of their unique juxtaposition to microvascular endothelium, lung PDGFRβ+cells are well situated to detect proinflammatory molecules released following epithelial injury and promote acute inflammatory responses. Thus we hypothesized that these cells represent an unrecognized immune surveillance or injury-sentinel interstitial cell. To evaluate this hypothesis, we isolated PDGFRβ+cells from murine lung and demonstrated that they have characteristics consistent with a pericyte population (referred to as pericyte-like cells for simplicity hereafter). We showed that pericyte-like cells expressed functional Toll-like receptors and upregulated chemokine expression following exposure to bronchoalveolar lavage fluid (BALF) collected from mice with sterile lung injury. Interestingly, BALF from mice without lung injury also induced chemokine expression in pericyte-like cells, suggesting that pericyte-like cells are primed to sense epithelial injury (permeability changes). Following LPS-induced lung inflammation, increased numbers of pericyte-like cells expressed IL-6, chemokine (C-X-C motif) ligand-1, chemokine (C-C motif) ligand 2/ monocyte chemotactic protein-1, and ICAM-1 in vivo. Sterile lung injury in pericyte-ablated mice was associated with decreased inflammation compared with normal mice. In summary, we found that pericyte-like cells are immune responsive and express diverse chemokines in response to lung injury in vitro and in vivo. Furthermore, pericyte-like cell ablation attenuated inflammation in sterile lung injury, suggesting that these cells play an important functional role in mediating lung inflammatory responses. We propose a model in which pericyte-like cells function as interstitial immune sentinels, detecting proinflammatory molecules released following epithelial barrier damage and participating in recruitment of circulating leukocytes.
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Chi F
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Mittelsteadt
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Rena
authors.initials: R
authors.lastname: Brauer
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: McKinney
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Schnapp
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.|Department of Pathology, University of Washington, Seattle, Washington.|Department of Global Health, University of Washington, Seattle, Washington; and.|Department of Pharmacology, University of Washington, Seattle, Washington.
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.affiliation: Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.affiliation: Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington; billa@uw.edu.|Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D007107:Immune System / Q000166:cytology*; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D055370:Lung Injury / Q000473:pathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: acute lung injury; damage-associated molecular patterns; inflammation; innate immunity; pericytes