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Innate imprinting of murine resident alveolar macrophages by allergic bronchial inflammation causes a switch from hypoinflammatory to hyperinflammatory reactivity

(2012) AMERICAN JOURNAL OF PATHOLOGY. 181(1). p.174-184
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Abstract
Resident alveolar macrophages (rAMs) residing in the bronchoalveolar lumen of the airways play an important role in limiting excessive inflammatory responses in the respiratory tract High phagocytic activity along with hyporesponsiveness to inflammatory insults and lack of autonomous IFN-beta production are crucial assets in this regulatory function. Using a mouse model of asthma, we analyzed the fate of rAMs both during and after allergic bronchial inflammation. Although nearly indistinguishable phenotypically from naive rAMs, postinflammation rAMs exhibited a strongly reduced basal phagocytic capacity, accompanied by a markedly increased inflammatory reactivity to Toll-like receptors TLR-3 (poly I:C), TLR-4 [lipopolysaccharide (LPS)], and TLR-7 (imiquimod). Importantly, after inflammation, rAMs exhibited a switch from an IFN-beta-defective to an IFN-beta-competent phenotype, thus indicating the occurrence of a new, inflammatory-released rAM population in the postallergic lung. Analysis of rAM turnover revealed a rapid disappearance of naive rAMs after the onset of inflammation. This inflammation-induced rAM turnover is critical for the development of the hyperinflammatory rAM phenotype observed after clearance of bronchial inflammation. These data document a novel mechanism of innate imprinting in which noninfectious bronchial inflammation causes alveolar macrophages to acquire a highly modified innate reactivity. The resulting increase in secretion of inflammatory mediators on TLR stimulation implies a role for this phenomenon of innate imprinting in the increased sensitivity of postallergic lungs to inflammatory insults. (Am J Pathol 2012, 181:174-184; http://dx.doi.org/10.1016/j.ajpath.2012.03.015)
Keywords
RESPIRATORY-TRACT, PULMONARY DENDRITIC CELLS, ALTERNATIVE ACTIVATION, LUNG MACROPHAGES, IMMUNE-RESPONSE, MICE, DISEASE, ASTHMA, HETEROGENEITY, ELIMINATION

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Chicago
Naessens, Thomas, Seppe Vander Beken, Pieter Bogaert, Nico Van Rooijen, Stefan Lienenklaus, Siegfried Weiss, Stefaan De Koker, and Johan Grooten. 2012. “Innate Imprinting of Murine Resident Alveolar Macrophages by Allergic Bronchial Inflammation Causes a Switch from Hypoinflammatory to Hyperinflammatory Reactivity.” American Journal of Pathology 181 (1): 174–184.
APA
Naessens, T., Vander Beken, S., Bogaert, P., Van Rooijen, N., Lienenklaus, S., Weiss, S., De Koker, S., et al. (2012). Innate imprinting of murine resident alveolar macrophages by allergic bronchial inflammation causes a switch from hypoinflammatory to hyperinflammatory reactivity. AMERICAN JOURNAL OF PATHOLOGY, 181(1), 174–184.
Vancouver
1.
Naessens T, Vander Beken S, Bogaert P, Van Rooijen N, Lienenklaus S, Weiss S, et al. Innate imprinting of murine resident alveolar macrophages by allergic bronchial inflammation causes a switch from hypoinflammatory to hyperinflammatory reactivity. AMERICAN JOURNAL OF PATHOLOGY. 2012;181(1):174–84.
MLA
Naessens, Thomas, Seppe Vander Beken, Pieter Bogaert, et al. “Innate Imprinting of Murine Resident Alveolar Macrophages by Allergic Bronchial Inflammation Causes a Switch from Hypoinflammatory to Hyperinflammatory Reactivity.” AMERICAN JOURNAL OF PATHOLOGY 181.1 (2012): 174–184. Print.
@article{2968115,
  abstract     = {Resident alveolar macrophages (rAMs) residing in the bronchoalveolar lumen of the airways play an important role in limiting excessive inflammatory responses in the respiratory tract High phagocytic activity along with hyporesponsiveness to inflammatory insults and lack of autonomous IFN-beta production are crucial assets in this regulatory function. Using a mouse model of asthma, we analyzed the fate of rAMs both during and after allergic bronchial inflammation. Although nearly indistinguishable phenotypically from naive rAMs, postinflammation rAMs exhibited a strongly reduced basal phagocytic capacity, accompanied by a markedly increased inflammatory reactivity to Toll-like receptors TLR-3 (poly I:C), TLR-4 [lipopolysaccharide (LPS)], and TLR-7 (imiquimod). Importantly, after inflammation, rAMs exhibited a switch from an IFN-beta-defective to an IFN-beta-competent phenotype, thus indicating the occurrence of a new, inflammatory-released rAM population in the postallergic lung. Analysis of rAM turnover revealed a rapid disappearance of naive rAMs after the onset of inflammation. This inflammation-induced rAM turnover is critical for the development of the hyperinflammatory rAM phenotype observed after clearance of bronchial inflammation. These data document a novel mechanism of innate imprinting in which noninfectious bronchial inflammation causes alveolar macrophages to acquire a highly modified innate reactivity. The resulting increase in secretion of inflammatory mediators on TLR stimulation implies a role for this phenomenon of innate imprinting in the increased sensitivity of postallergic lungs to inflammatory insults. (Am J Pathol 2012, 181:174-184; http://dx.doi.org/10.1016/j.ajpath.2012.03.015)},
  author       = {Naessens, Thomas and Vander Beken, Seppe and Bogaert, Pieter and Van Rooijen, Nico and Lienenklaus, Stefan and Weiss, Siegfried and De Koker, Stefaan and Grooten, Johan},
  issn         = {0002-9440},
  journal      = {AMERICAN JOURNAL OF PATHOLOGY},
  keyword      = {RESPIRATORY-TRACT,PULMONARY DENDRITIC CELLS,ALTERNATIVE ACTIVATION,LUNG MACROPHAGES,IMMUNE-RESPONSE,MICE,DISEASE,ASTHMA,HETEROGENEITY,ELIMINATION},
  language     = {eng},
  number       = {1},
  pages        = {174--184},
  title        = {Innate imprinting of murine resident alveolar macrophages by allergic bronchial inflammation causes a switch from hypoinflammatory to hyperinflammatory reactivity},
  url          = {http://dx.doi.org/10.1016/j.ajpath.2012.03.015},
  volume       = {181},
  year         = {2012},
}

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