Abstract |
Macrophages play a central role in immune and tissue responses of granulomatous lung diseases induced by pathogens and foreign bodies. Circulating monocytes are generally viewed as central precursors of these tissue effector macrophages. Here, we provide evidence that granulomas derive from alveolar macrophages serving as a local reservoir for the expansion of activated phagocytic macrophages. By exploring lung granulomatous responses to silica particles in IL-1-deficient mice, we found that the absence of IL-1α, but not IL-1β, was associated with reduced CD11b(high) phagocytic macrophage accumulation and fewer granulomas. This defect was associated with impaired alveolar clearance and resulted in the development of pulmonary alveolar proteinosis (PAP). Reconstitution of IL-1α(-/-) mice with recombinant IL-1α restored lung clearance functions and the pulmonary accumulation of CD11b(high) phagocytic macrophages. Mechanistically, IL-1α induced the proliferation of CD11b(low) alveolar macrophages and differentiated these cells into CD11b(high) macrophages which perform critical phagocytic functions and organize granuloma. We newly discovered here that IL-1α triggers lung responses requiring macrophage proliferation and maturation from tissue-resident macrophages.
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Authors | François Huaux, Sandra Lo Re, Giulia Giordano, Francine Uwambayinema, Raynal Devosse, Yousof Yakoub, Nadtha Panin, Mihaly Palmai-Pallag, Virginie Rabolli, Monique Delos, Etienne Marbaix, Nicolas Dauguet, Isabelle Couillin, Bernhard Ryffel, Jean-Christophe Renauld, Dominique Lison |
Journal | The Journal of pathology
(J Pathol)
Vol. 235
Issue 5
Pg. 698-709
(Apr 2015)
ISSN: 1096-9896 [Electronic] England |
PMID | 25421226
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
Chemical References |
- CD11b Antigen
- IL1B protein, mouse
- Interleukin-1alpha
- Interleukin-1beta
- Silicon Dioxide
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Topics |
- Animals
- CD11b Antigen
(metabolism)
- Cell Proliferation
- Cells, Cultured
- Disease Models, Animal
- Granuloma
(chemically induced, genetics, metabolism, pathology)
- Interleukin-1alpha
(deficiency, genetics, metabolism)
- Interleukin-1beta
(genetics, metabolism)
- Lung Diseases
(chemically induced, genetics, metabolism, pathology)
- Macrophage Activation
- Macrophages, Alveolar
(metabolism, pathology)
- Mice, Knockout
- Phagocytosis
- Phenotype
- Pulmonary Alveolar Proteinosis
(chemically induced, genetics, metabolism, pathology)
- Silicon Dioxide
- Time Factors
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