Neutrophils as early immunologic effectors in hemorrhage-or endotoxemia-induced acute lung injury

E Abraham, A Carmody, R Shenkar… - American Journal of …, 2000 - journals.physiology.org
E Abraham, A Carmody, R Shenkar, J Arcaroli
American Journal of Physiology-Lung Cellular and Molecular …, 2000journals.physiology.org
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-κB after …
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-κB 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-1β (IL-1β), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1β, MIP-2, and TNF-α were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1β and MIP-2 but not in TNF-α expression in the lungs after endotoxemia. These experiments show that neutrophils play a centrol role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.
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