Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9470
Title: TNF alpha inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation
Authors: Borges, Valeria de Matos
Vandivier, R. William
McPhillips, Kathleen A.
Kench, Jennifer A.
Morimoto, Konosuke
Groshong, Steve D.
Richens, Tiffany R.
Graham, Brian B.
Muldrow, Alaina M.
Van Heule, Lea
Henson, Peter M.
Janssen, William J.
Affilliation: Department of Pediatrics. Program in Cell Biology. Denver, Colorado / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.
National Jewish Health. Department of Medicine. Denver, Colorado, USA.
Department of Pediatrics. Program in Cell Biology. Denver, Colorado, USA.
Department of Pediatrics. Program in Cell Biology. Denver, Colorado, USA.
University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Department of Medicine. Denver, Colorado, USA / Institute of Tropical Medicine. Nagasaki University. Department of Clinical Medicine. Nagasaki, Japan.
National Jewish Health. Department of Medicine. Denver, Colorado, USA.
University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Department of Medicine. Denver, Colorado, USA.
University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Department of Medicine. Denver, Colorado, USA.
National Jewish Health. Department of Medicine. Denver, Colorado, USA.
National Jewish Health. Department of Medicine. Denver, Colorado, USA.
Department of Pediatrics. Program in Cell Biology. Denver, Colorado, USA.
National Jewish Health. Department of Medicine. Denver, Colorado, USA / University of Colorado Health Sciences Center. Division of Pulmonary Sciences and Critical Care Medicine. Department of Medicine. Denver, Colorado, USA.
Abstract: Efficient removal of apoptotic cells is essential for resolution of inflammation. Failure to clear dying cells can exacerbate lung injury and lead to persistent inflammation and autoimmunity. Here we show that TNFalpha blocks apoptotic cell clearance by alveolar macrophages and leads to proinflammatory responses in the lung. Compared with mice treated with intratracheal TNFalpha or exogenous apoptotic cells, mice treated with the combination of TNFalpha plus apoptotic cells demonstrated reduced apoptotic cell clearance from the lungs and increased recruitment of inflammatory leukocytes to the air spaces. Treatment with intratracheal TNFalpha had no effect on the removal of exogenous apoptotic cells from the lungs of TNFalpha receptor-1 (p55) and -2 (p75) double mutant mice and no effect on leukocyte recruitment. Bronchoalveolar lavage from mice treated with TNFalpha plus apoptotic cells contained increased levels of proinflammatory cytokines IL-6, KC, and MCP-1, but exhibited no change in levels of anti-inflammatory cytokines IL-10 and TGF-beta. Administration of TNFalpha plus apoptotic cells during LPS-induced lung injury augmented neutrophil accumulation and proinflammatory cytokine production. These findings suggest that the presence of TNFalpha in the lung can alter the response of phagocytes to apoptotic cells leading to inflammatory cell recruitment and proinflammatory mediator production.
Keywords: Apoptosis
Phagocytosis
DeCS: Apoptose/efeitos de drogas
Pulmão/patologia
Pneumonia/etiologia
Fator de Necrose Tumoral alfa/farmacologia
Animais
Ensaio de Imunoadsorção Enzimática
Feminino
Citometria de Fluxo
Inflamação/etiologia
Interleucina-10/metabolismo
Leucócitos/metabolismo
Lipopolissacarídeos/farmacologia
Pulmão/efeitos de drogas
Macrófagos Alveolares/citologia
Camundongos
Camundongos Endogâmicos BALB C
Neutrófilos/metabolismo
Fagocitose
Pneumonia/fisiopatologia
Receptores Tipo I de Fatores de Necrose Tumoral/fisiologia
Issue Date: 2009
Publisher: American Physiological Society
Citation: BORGES, V. M. et al. TNF alpha inhibits apoptotic cell clearance in the lung, exacerbating acute inflammation. American Journal Physiology Lung Cell Molecular Physiology, v. 297, n. 4, p. 586-595, 2009.
DOI: 10.1152/ajplung.90569.2008
ISSN: 1522-1504
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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