title: IL-1α induces CD11b(low) alveolar macrophage proliferation and maturation during granuloma formation.
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.
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Experimentale et Clinique (IREC), Université catholique de Louvain, Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Huaux
authors.forename: Sandra
authors.initials: S
authors.lastname: Lo Re
authors.forename: Giulia
authors.initials: G
authors.lastname: Giordano
authors.forename: Francine
authors.initials: F
authors.lastname: Uwambayinema
authors.forename: Raynal
authors.initials: R
authors.lastname: Devosse
authors.forename: Yousof
authors.initials: Y
authors.lastname: Yakoub
authors.forename: Nadtha
authors.initials: N
authors.lastname: Panin
authors.forename: Mihaly
authors.initials: M
authors.lastname: Palmai-Pallag
authors.forename: Virginie
authors.initials: V
authors.lastname: Rabolli
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dauguet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Couillin
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006099:Granuloma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053582:Interleukin-1alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D010587:Phagocytosis; D010641:Phenotype; D011649:Pulmonary Alveolar Proteinosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012822:Silicon Dioxide; D013997:Time Factors
chemical_list: D039481:CD11b Antigen; C587672:IL1B protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D012822:Silicon Dioxide
keywords: IL-1α; granuloma; macrophage proliferation; particles; pulmonary alveolar proteinosis