Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO
MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the...
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| Language: | English |
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Wiley
2014-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2014/304180 |
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| author | Rupa Biswas Raymond F. Hamilton Andrij Holian |
| author_facet | Rupa Biswas Raymond F. Hamilton Andrij Holian |
| author_sort | Rupa Biswas |
| collection | DOAJ |
| description | MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO−/− AM compared to wild type (WT) AM. Furthermore, in MARCO−/− AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP. |
| format | Article |
| id | doaj-art-3f45d1ec34474ab891eb3efbb7f3ef2f |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-3f45d1ec34474ab891eb3efbb7f3ef2f2025-02-03T00:59:20ZengWileyJournal of Immunology Research2314-88612314-71562014-01-01201410.1155/2014/304180304180Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCORupa Biswas0Raymond F. Hamilton1Andrij Holian2Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USACenter for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USACenter for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USAMARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO−/− AM compared to wild type (WT) AM. Furthermore, in MARCO−/− AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.http://dx.doi.org/10.1155/2014/304180 |
| spellingShingle | Rupa Biswas Raymond F. Hamilton Andrij Holian Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO Journal of Immunology Research |
| title | Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO |
| title_full | Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO |
| title_fullStr | Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO |
| title_full_unstemmed | Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO |
| title_short | Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO |
| title_sort | role of lysosomes in silica induced inflammasome activation and inflammation in absence of marco |
| url | http://dx.doi.org/10.1155/2014/304180 |
| work_keys_str_mv | AT rupabiswas roleoflysosomesinsilicainducedinflammasomeactivationandinflammationinabsenceofmarco AT raymondfhamilton roleoflysosomesinsilicainducedinflammasomeactivationandinflammationinabsenceofmarco AT andrijholian roleoflysosomesinsilicainducedinflammasomeactivationandinflammationinabsenceofmarco |