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IL ‐1α induces CD11b low alveolar macrophage proliferation and maturation during granuloma formation
Author(s) -
Huaux François,
Lo Re Sandra,
Giordano Giulia,
Uwambayinema Francine,
Devosse Raynal,
Yakoub Yousof,
Panin Nadtha,
PalmaiPallag Mihaly,
Rabolli Virginie,
Delos Monique,
Marbaix Etienne,
Dauguet Nicolas,
Couillin Isabelle,
Ryffel Bernhard,
Renauld JeanChristophe,
Lison Dominique
Publication year - 2015
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4487
Subject(s) - macrophage , integrin alpha m , alveolar macrophage , lung , immunology , granuloma , pulmonary alveolus , phagocytosis , immune system , phagosome , inflammation , microbiology and biotechnology , biology , chemistry , pathology , medicine , in vitro , biochemistry
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. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.