Neutrophils are major contributors to intraparenchymal lung IL-1 beta expression after hemorrhage and endotoxemia.
Acute lung injury and the acute respiratory distress syndrome (ARDS) are significant causes of morbidity and mortality following sepsis and hemorrhage. Increased IL-1beta production in the lung is important in the development of acute inflammatory lung injury. Although neutrophils are an important component of the inflammatory response that characterizes acute lung injury, there is little information to suggest that they are capable of initiating cytokine-mediated immune responses in the lung. To explore the role of neutrophils in the early stages of acute lung injury, we examined IL-1beta production by mouse lung neutrophils after hemorrhage and endotoxemia. There was a significant increase in IL-1beta expression among intraparenchymal pulmonary neutrophil/mononuclear cells (IPNMC) 1 h after hemorrhage or endotoxemia. IL-1beta was detected only in a neutrophil-rich fraction of the IPNMC, but not in T and B lymphocytes positively selected from the IPNMC. Cyclophosphamide (CTX)-treated neutropenic mice expressed significantly less IL-1beta in IPNMC after hemorrhage or endotoxemia compared with CTX-untreated controls. Immunohistochemical analysis of lung sections from mice after hemorrhage or endotoxemia revealed IL-1beta expression in infiltrating neutrophils. These data indicate that IL-1beta-producing neutrophils traffic to the lungs rapidly in response to hemorrhage or endotoxemia and support the concept that proinflammatory cytokine production by lung neutrophils may contribute to the development of lung injury after blood loss and sepsis.
Parsey
M V
MV
Department of Pulmonary and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Tuder
R M
RM
Abraham
E
E
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006470:Hemorrhage / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*
D007375:Interleukin-1