The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin
Abstract Cell‐free hemoglobin (CFH) is associated with severe lung injury in human patients and is sufficient to induce airspace inflammation and alveolar–capillary barrier dysfunction in an experimental model of acute lung injury. The mechanisms through which this occurs are unknown. One key pathwa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-11-01
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| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.14589 |
| _version_ | 1818205067194400768 |
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| author | Ciara M. Shaver Stuart R. Landstreet Sangamithra Pugazenthi Fiona Scott Nathan Putz Lorraine B. Ware Julie A. Bastarache |
| author_facet | Ciara M. Shaver Stuart R. Landstreet Sangamithra Pugazenthi Fiona Scott Nathan Putz Lorraine B. Ware Julie A. Bastarache |
| author_sort | Ciara M. Shaver |
| collection | DOAJ |
| description | Abstract Cell‐free hemoglobin (CFH) is associated with severe lung injury in human patients and is sufficient to induce airspace inflammation and alveolar–capillary barrier dysfunction in an experimental model of acute lung injury. The mechanisms through which this occurs are unknown. One key pathway which regulates inflammation during acute lung injury is the NLRP3 inflammasome. Because CFH can act as a damage‐associated molecular pattern, we hypothesized that CFH may activate the NLRP3 inflammasome during acute lung injury. Primary mouse alveolar macrophages and cultured murine macrophages exposed to CFH (0–1 mg/ml) for 24 hr demonstrated robust upregulation of the NLRP3 inflammasome components NLRP3, caspase‐1, and caspase‐11. Maximal induction of the NLRP3 inflammasome by CFH required TLR4. Compared to wild‐type controls, mice lacking NLRP3 developed less airspace inflammation (2.7 × 105 cells/ml in bronchoalveolar lavage fluid versus. 1.1 × 105/ml, p = .006) after exposure to intratracheal CFH. Together, these data demonstrate that CFH can stimulate the NLRP3 inflammasome in macrophages and that this pathway may be important in the pathogenesis of CFH‐induced acute lung injury. |
| first_indexed | 2024-12-12T03:51:14Z |
| format | Article |
| id | doaj.art-38bde6fc94dd4153850cee25b801e450 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-12T03:51:14Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-38bde6fc94dd4153850cee25b801e4502022-12-22T00:39:22ZengWileyPhysiological Reports2051-817X2020-11-01821n/an/a10.14814/phy2.14589The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobinCiara M. Shaver0Stuart R. Landstreet1Sangamithra Pugazenthi2Fiona Scott3Nathan Putz4Lorraine B. Ware5Julie A. Bastarache6Division of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USADivision of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USAVanderbilt University Nashville TN USADivision of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USADivision of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USADivision of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USADivision of Allergy, Pulmonary, and Critical Care Medicine Department of Medicine Vanderbilt University Medical Center Nashville TN USAAbstract Cell‐free hemoglobin (CFH) is associated with severe lung injury in human patients and is sufficient to induce airspace inflammation and alveolar–capillary barrier dysfunction in an experimental model of acute lung injury. The mechanisms through which this occurs are unknown. One key pathway which regulates inflammation during acute lung injury is the NLRP3 inflammasome. Because CFH can act as a damage‐associated molecular pattern, we hypothesized that CFH may activate the NLRP3 inflammasome during acute lung injury. Primary mouse alveolar macrophages and cultured murine macrophages exposed to CFH (0–1 mg/ml) for 24 hr demonstrated robust upregulation of the NLRP3 inflammasome components NLRP3, caspase‐1, and caspase‐11. Maximal induction of the NLRP3 inflammasome by CFH required TLR4. Compared to wild‐type controls, mice lacking NLRP3 developed less airspace inflammation (2.7 × 105 cells/ml in bronchoalveolar lavage fluid versus. 1.1 × 105/ml, p = .006) after exposure to intratracheal CFH. Together, these data demonstrate that CFH can stimulate the NLRP3 inflammasome in macrophages and that this pathway may be important in the pathogenesis of CFH‐induced acute lung injury.https://doi.org/10.14814/phy2.14589acute lung injuryARDScell‐free hemoglobininflammasomeNLRP3 |
| spellingShingle | Ciara M. Shaver Stuart R. Landstreet Sangamithra Pugazenthi Fiona Scott Nathan Putz Lorraine B. Ware Julie A. Bastarache The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin Physiological Reports acute lung injury ARDS cell‐free hemoglobin inflammasome NLRP3 |
| title | The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin |
| title_full | The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin |
| title_fullStr | The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin |
| title_full_unstemmed | The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin |
| title_short | The NLRP3 inflammasome in macrophages is stimulated by cell‐free hemoglobin |
| title_sort | nlrp3 inflammasome in macrophages is stimulated by cell free hemoglobin |
| topic | acute lung injury ARDS cell‐free hemoglobin inflammasome NLRP3 |
| url | https://doi.org/10.14814/phy2.14589 |
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