Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes
Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/946878 |
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| author | Rafael L. Simões Maria Augusta Arruda Cláudio Canetti Carlos H. Serezani Iolanda M. Fierro Christina Barja-Fidalgo |
| author_facet | Rafael L. Simões Maria Augusta Arruda Cláudio Canetti Carlos H. Serezani Iolanda M. Fierro Christina Barja-Fidalgo |
| author_sort | Rafael L. Simões |
| collection | DOAJ |
| description | Clinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM) elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS) and nitric oxide (NO) generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes. |
| format | Article |
| id | doaj-art-1ec1bcec84304d59862b6f436db399eb |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1ec1bcec84304d59862b6f436db399eb2025-02-03T01:27:31ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/946878946878Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic EpisodesRafael L. Simões0Maria Augusta Arruda1Cláudio Canetti2Carlos H. Serezani3Iolanda M. Fierro4Christina Barja-Fidalgo5Laboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, Avenida 28 de Setembro, 87 Fundos, Vila Isabel, 20551-030 Rio de Janeiro, RJ, BrazilLaboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, Avenida 28 de Setembro, 87 Fundos, Vila Isabel, 20551-030 Rio de Janeiro, RJ, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 22541-900 Rio de Janeiro, RJ, BrazilDepartment of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USALaboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, Avenida 28 de Setembro, 87 Fundos, Vila Isabel, 20551-030 Rio de Janeiro, RJ, BrazilLaboratory of Cellular and Molecular Pharmacology, Department of Cell Biology, IBRAG, Avenida 28 de Setembro, 87 Fundos, Vila Isabel, 20551-030 Rio de Janeiro, RJ, BrazilClinical and experimental observations have supported the notion that free heme released during hemorrhagic and hemolytic episodes may have a major role in lung inflammation. With alveolar macrophages (AM) being the main line of defense in lung environments, the influence of free heme on AM activity and function was investigated. We observed that heme in a concentration range found during hemolytic episodes (3–30 μM) elicits AM to present a proinflammatory profile, stimulating reactive oxygen species (ROS) and nitric oxide (NO) generation and inducing IL-1β, IL-6, and IL-10 secretion. ROS production is NADPH oxidase-dependent, being inhibited by DPI and apocynin, and involves p47 subunit phosphorylation. Furthermore, heme induces NF-κB nuclear translocation, iNOS, and also HO-1 expression. Moreover, AM stimulated with free heme show enhanced phagocytic and bactericidal activities. Taken together, the data support a dual role for heme in the inflammatory response associated with lung hemorrhage, acting as a proinflammatory molecule that can either act as both an adjuvant of the innate immunity and as an amplifier of the inflammatory response, leading tissue injury. The understanding of heme effects on pulmonary inflammatory processes can lead to the development of new strategies to ameliorate tissue damage associated with hemorrhagic episodes.http://dx.doi.org/10.1155/2013/946878 |
| spellingShingle | Rafael L. Simões Maria Augusta Arruda Cláudio Canetti Carlos H. Serezani Iolanda M. Fierro Christina Barja-Fidalgo Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes Mediators of Inflammation |
| title | Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes |
| title_full | Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes |
| title_fullStr | Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes |
| title_full_unstemmed | Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes |
| title_short | Proinflammatory Responses of Heme in Alveolar Macrophages: Repercussion in Lung Hemorrhagic Episodes |
| title_sort | proinflammatory responses of heme in alveolar macrophages repercussion in lung hemorrhagic episodes |
| url | http://dx.doi.org/10.1155/2013/946878 |
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