Publication Date:
2014-01-28
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117212/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117212/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Westphalen, Kristin -- Gusarova, Galina A -- Islam, Mohammad N -- Subramanian, Manikandan -- Cohen, Taylor S -- Prince, Alice S -- Bhattacharya, Jahar -- HL57556/HL/NHLBI NIH HHS/ -- HL64896/HL/NHLBI NIH HHS/ -- HL73989/HL/NHLBI NIH HHS/ -- HL78645/HL/NHLBI NIH HHS/ -- R01 HL057556/HL/NHLBI NIH HHS/ -- R01 HL064896/HL/NHLBI NIH HHS/ -- R01 HL073989/HL/NHLBI NIH HHS/ -- R01 HL078645/HL/NHLBI NIH HHS/ -- R01 HL079395/HL/NHLBI NIH HHS/ -- England -- Nature. 2014 Feb 27;506(7489):503-6. doi: 10.1038/nature12902. Epub 2014 Jan 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York 10032, USA. ; Department of Medicine, Division of Molecular Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24463523" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Bronchoalveolar Lavage Fluid/immunology
;
Calcium/metabolism
;
Cell Adhesion
;
*Cell Communication
;
Connexin 43/deficiency/genetics/metabolism
;
Cytokines/immunology/secretion
;
Female
;
Gap Junctions/metabolism
;
Lipopolysaccharides/pharmacology
;
Macrophages, Alveolar/*cytology/*immunology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Neutrophil Infiltration
;
Neutrophils/immunology
;
Pneumonia/chemically induced/immunology/pathology
;
Pulmonary Alveoli/*cytology/*immunology
;
Respiratory Mucosa/*cytology/*immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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