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Am J Physiol Lung Cell Mol Physiol. 2017 Apr 1;312(4):L556-L567. doi: 10.1152/ajplung.00349.2016. Epub 2017 Feb 10.

Lung pericyte-like cells are functional interstitial immune sentinel cells.

Author information

1
Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington.
2
Department of Pathology, University of Washington, Seattle, Washington.
3
Department of Global Health, University of Washington, Seattle, Washington; and.
4
Department of Pharmacology, University of Washington, Seattle, Washington.
5
Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington.
6
Center for Lung Biology, Department of Medicine, University of Washington, Seattle, Washington; billa@uw.edu.

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.

KEYWORDS:

acute lung injury; damage-associated molecular patterns; inflammation; innate immunity; pericytes

PMID:
28188224
PMCID:
PMC5407093
DOI:
10.1152/ajplung.00349.2016
[Indexed for MEDLINE]
Free PMC Article

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