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Neutrophil sequestration in rat lungs.
  1. G M Brown,
  2. D M Brown,
  3. K Donaldson,
  4. E Drost,
  5. W MacNee
  1. Institute of Occupational Medicine, Edinburg, UK.

    Abstract

    BACKGROUND--The transit of neutrophils through the pulmonary microvasculature is prolonged compared with red blood cells and is increased further during cigarette smoking and in exacerbations of chronic obstructive pulmonary disease. The increased residence time (sequestration) of neutrophils in the pulmonary capillaries in these conditions may be the first step leading to the accumulation of cells within the lung interstitium and in the bronchoalveolar space, so potentiating lung damage. A rat model has been developed to investigate the factors which may influence neutrophil transit through the lung microvasculature. METHODS--Intratracheal instillation of the heat killed organism Corynebacterium parvum was used to induce an acute neutrophil alveolitis. Neutrophils and red blood cells were isolated from donor rats, labelled with two distinct radioisotopes, and then reinjected into recipient rats to assess their transit through the pulmonary circulation. To ascertain whether peripheral blood neutrophils were minimally altered by the isolation procedure their functional status in vitro was compared with that of inflammatory neutrophils in a number of assays commonly used as descriptors of neutrophil activation. The influence of neutrophil activation on the accumulation of cells in the lungs was assessed by comparing the lung sequestration of control neutrophils, isolated from peripheral blood, with that of inflammatory neutrophils obtained from bronchoalveolar lavage of inflamed rat lungs. Lung sequestration of neutrophils was defined as the fold increase in the ratio of neutrophils labelled with chromium-51 to red blood cells labelled with technetium-99m in lung tissue compared with the same ratio in peripheral blood. RESULTS--Sequestration of peripheral blood neutrophils occurred in control rat lungs as shown by a 17.5 (2.1) fold increase in the ratio of neutrophils to red blood cells in the pulmonary circulation compared with the ratio of these cells in the peripheral circulation. When inflammatory neutrophils, obtained by bronchoalveolar lavage from C parvum-treated animals, were injected into control rats, the increase was 90.6 (11.0) fold. Induction of an inflammatory response in the lung tissue of the recipient rat also caused an increase in the sequestration of control neutrophils compared with the same cells in control rat lungs which was, however, less marked than when inflammatory neutrophils were used (34.7 (4.7) fold). The mean (SE) pressure developed on filtration of inflammatory neutrophils in vitro through a millipore filter (7.53 (0.2) cm H2O) was greater than that of peripheral blood neutrophils (1.18 (0.2) cm H2O). Increased filtration pressure indicates a decrease in cell deformability and suggests that this may be a contributory factor to the increased sequestration of inflammatory neutrophils in the pulmonary vasculature. CONCLUSIONS--This study shows that there is sequestration of neutrophils in the pulmonary vasculature in normal rat lungs which increases in acute lung inflammation and when inflammatory neutrophils are injected into control animals. In this model changes in the neutrophil, such as cell deformability, may have a more important role in inducing increased neutrophil sequestration than the inflammatory response in the lungs.

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