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Nature. 2014 Feb 27;506(7489):503-6. doi: 10.1038/nature12902. Epub 2014 Jan 19.

Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity.

Author information

1
Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York 10032, USA.
2
Department of Medicine, Division of Molecular Medicine, Columbia University Medical Center, New York, New York 10032, USA.
3
Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA.
4
1] Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Physiology & Cellular Biophysics, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York 10032, USA.

Abstract

The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca(2+) waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

PMID:
24463523
PMCID:
PMC4117212
DOI:
10.1038/nature12902
[Indexed for MEDLINE]
Free PMC Article
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