| First Author | Poczobutt JM | Year | 2021 |
| Journal | Am J Respir Cell Mol Biol | Volume | 64 |
| Issue | 5 | Pages | 629-640 |
| PubMed ID | 33662226 | Mgi Jnum | J:326383 |
| Mgi Id | MGI:7311826 | Doi | 10.1165/rcmb.2020-0229OC |
| Citation | Poczobutt JM, et al. (2021) Altered Macrophage Function Associated with Crystalline Lung Inflammation in Acid Sphingomyelinase Deficiency. Am J Respir Cell Mol Biol 64(5):629-640 |
| abstractText | 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. |
