Altered Macrophage Function Associated with Crystalline Lung Inflammation in Acid Sphingomyelinase Deficiency
dc.contributor.author | Poczobutt, Joanna M. | |
dc.contributor.author | Mikosz, Andrew M. | |
dc.contributor.author | Poirier, Christophe | |
dc.contributor.author | Beatman, Erica L. | |
dc.contributor.author | Serban, Karina A. | |
dc.contributor.author | Gally, Fabienne | |
dc.contributor.author | Cao, Danting | |
dc.contributor.author | McCubbrey, Alexandra L. | |
dc.contributor.author | Cornell, Christina F. | |
dc.contributor.author | Schweitzer, Kelly S. | |
dc.contributor.author | Berdyshev, Evgeny V. | |
dc.contributor.author | Bronova, Irina A. | |
dc.contributor.author | Paris, François | |
dc.contributor.author | Petrache, Irina | |
dc.contributor.department | Medicine, School of Medicine | |
dc.date.accessioned | 2024-03-26T14:56:20Z | |
dc.date.available | 2024-03-26T14:56:20Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Deficiency of ASM (acid sphingomyelinase) causes the lysosomal storage Niemann-Pick disease (NPD). Patients with NPD type B may develop progressive interstitial lung disease with frequent respiratory infections. Although several investigations using the ASM-deficient (ASMKO) mouse NPD model revealed inflammation and foamy macrophages, there is little insight into the pathogenesis of NPD-associated lung disease. Using ASMKO mice, we report that ASM deficiency is associated with a complex inflammatory phenotype characterized by marked accumulation of monocyte-derived CD11b+ macrophages and expansion of airspace/alveolar CD11c+ CD11b− macrophages, both with increased size, granularity, and foaminess. Both the alternative and classical pathways were activated, with decreased in situ phagocytosis of opsonized (Fc-coated) targets, preserved clearance of apoptotic cells (efferocytosis), secretion of Th2 cytokines, increased CD11c+/CD11b+ cells, and more than a twofold increase in lung and plasma proinflammatory cytokines. Macrophages, neutrophils, eosinophils, and noninflammatory lung cells of ASMKO lungs also exhibited marked accumulation of chitinase-like protein Ym1/2, which formed large eosinophilic polygonal Charcot-Leyden–like crystals. In addition to providing insight into novel features of lung inflammation that may be associated with NPD, our report provides a novel connection between ASM and the development of crystal-associated lung inflammation with alterations in macrophage biology. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Poczobutt JM, Mikosz AM, Poirier C, et al. Altered Macrophage Function Associated with Crystalline Lung Inflammation in Acid Sphingomyelinase Deficiency. Am J Respir Cell Mol Biol. 2021;64(5):629-640. doi:10.1165/rcmb.2020-0229OC | |
dc.identifier.uri | https://hdl.handle.net/1805/39537 | |
dc.language.iso | en_US | |
dc.publisher | American Thoracic Society | |
dc.relation.isversionof | 10.1165/rcmb.2020-0229OC | |
dc.relation.journal | American Journal of Respiratory Cell and Molecular Biology | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Sphingomyelinase | |
dc.subject | Macrophages | |
dc.subject | Chitinases | |
dc.subject | Inflammation | |
dc.subject | Neutrophils | |
dc.title | Altered Macrophage Function Associated with Crystalline Lung Inflammation in Acid Sphingomyelinase Deficiency | |
dc.type | Article | |
ul.alternative.fulltext | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086042/ |