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Prevention of pulmonary injury in isolated perfused rat lungs by activated
human neutrophils preincubated with anti-Mo1 monoclonal antibody
G Ismail, ML Morganroth, RF Todd and LA Boxer
Neutrophil activation results in neutrophil adherence and may subsequently
cause lung injury through the generation of oxidants, release of granule
proteases, and generation of a variety of mediator substances. We
hypothesized that inhibition of neutrophil adherence and subsequent lung
sequestration would attenuate the lung injury caused by activated
neutrophils. Using isolated perfused rat lungs, we determined if anti-Mo1
monoclonal antibody (binds to the alpha subunit of a neutrophil
glycoprotein [gp 155.94] that facilitates adherence) would attenuate lung
neutrophil sequestration and lung injury caused by human neutrophils
stimulated by phorbol myristate acetate (PMA). PMA- stimulated neutrophils
but not PMA or neutrophils alone caused lung injury as assessed by
accumulation of 125I-bovine serum albumin into lung parenchyma and alveolar
lavage fluid. Incubation of neutrophils with anti-Mo1 antibody prior to
stimulation with PMA attenuated lung injury and neutrophil sequestration.
Furthermore, a histological survey revealed that anti-Mo1 antibody
inhibited neutrophils present in the lung from spreading following exposure
to PMA. Anti-Mo1 antibody did not inhibit PMA-stimulated neutrophil release
of granule constituents or toxic O2 metabolites as evidenced by lysozyme
and lactoferrin release or the reduction of ferricytochrome c in the lung
perfusate. The inhibition of lung injury caused by the anti-Mo1 antibody
was not likely due to a nonspecific effect of the antibody, since another
murine monoclonal antibody of the same class (anti-Mo5) did not inhibit
lung neutrophil sequestration or lung injury. Thus, in this experimental
model, interference with the close approximation of the neutrophil to its
target site inhibited the ability of the activated human neutrophil to
cause injury.
Volume 69,
Issue 4,
pp. 1167-1174,
04/01/1987
Copyright © 1987 by The American Society of Hematology

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