Role of CC Chemokine Receptor 4 in Natural Killer Cell Activation during Acute Cigarette Smoke Exposure
| Autor: | Brian E. Martin, Peter Mancuso, Michal A. Olszewski, Christine M. Freeman, Valerie R. Stolberg, Stephen W. Chensue, Jeffrey L. Curtis |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Receptors CCR4 Time Factors chemical and pharmacologic phenomena Cell Communication Lung injury Biology Ligands Lymphocyte Activation Pathology and Forensic Medicine Gene Knockout Techniques Mice medicine CXCL10 Animals Interferon gamma RNA Messenger Lung Innate immune system Macrophages Smoking Histocompatibility Antigens Class II Membrane Proteins hemic and immune systems Regular Article Dendritic Cells NKG2D Molecular biology Immunity Innate CD11c Antigen Killer Cells Natural Mice Inbred C57BL Immunology Interleukin 12 Female CC chemokine receptors Natural killer cell activation medicine.drug |
| Zdroj: | The American Journal of Pathology. 184(2):454-463 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2013.10.017 |
| Popis: | Cigarette smoke (CS)-induced lung injury involves innate immune responses. The activation of innate effector cells is thought to require cross talk with dendritic cells (DCs) and macrophages, but the mediators of interaction are unknown. One candidate, CC chemokine receptor 4 (CCR4), is expressed by innate and adaptive effector cells, and its ligands are produced by DCs and macrophages. Using flow cytometry and confocal microscopy, we defined innate responses of lung myeloid DCs, macrophages, and conventional natural killer (NK) cells in mice exposed to CS over 4 days and examined the contribution of CCR4 using CCR4 knockout (CCR4(-/-)) mice. CS affected populations differently, causing an increase in F4/80(+) macrophages, a reduction in parenchymal CD11c(+)CD11b(+)CD103(-) DCs, but no effect on mucosal CD11c(+)CD11b(-)CD103(+) DCs. CS also induced a population of primed/activated CD69(+) NK cells and bronchoepithelial expression of the stress-related NKG2D receptor-activating protein, retinoic acid early transcript 1. CS-exposed CCR4(-/-) mice were similar to controls regarding effects on DCs and macrophages but displayed substantially impaired NK priming/activation and reduced expression of transcripts for interferon gamma, CXCL10, and retinoic acid early transcript 1. Quantitative confocal microscopy revealed that lungs of CS-exposed CCR4(-/-) mice had significantly reduced contacts of NK cells with CD11c(+) cells. These findings demonstrate that acute CS exposure elicits NK cell responses and suggest that CCR4 promotes NK cell priming/activation by mediating contacts with sentinel cells in the lung. |
| Databáze: | OpenAIRE |
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