title: Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.
abstract: Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.
authors.affiliation: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. edward.abraham@uchsc.edu
authors.forename: E
authors.initials: E
authors.lastname: Abraham
authors.forename: A
authors.initials: A
authors.lastname: Carmody
authors.forename: R
authors.initials: R
authors.lastname: Shenkar
authors.forename: J
authors.initials: J
authors.lastname: Arcaroli
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D006469:Hemoptysis / Q000276:immunology*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009503:Neutropenia / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009195:Peroxidase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase