The authors studied the effects of increase and/or depletion of neutrophils on the endotoxin-induced lung injury. A single bolus of sublethal dose of endotoxin was injected to the male Sprague-Dawley rats, which received splenectomy and/or
nitrogen
mustard-injection(0.175mg/100g) 3 days before endotoxin(0.5mg/100g) administration. Lung tissues were extracted at 1, 4, 8 and 24 hours after endotoxin administration and examined by the light, transmission, and scanning electron microscopes.
Enzyme
cytochemical electron microscopic study using horseradiase to clatify the permeability changes of pulmonary microvasulature was also done.
@ES The results obtained were summarized as follow:
@EN In the endotoxin injected without any additional measured groups, many neutrophils, platelets and a few mononuclear cells were sequestered in the lumina of alveolar capillaries at 1 capillaries at 1 hour after endotoxin injection. After than,
the
inflammatory cells were infiltrated to interstitial and alveolar spaces. The endothelial cells of pulmonary capillaries revealed increase of pinocytotic vesicles, cytoplasmic edema and formation of irregular
cytoplasmic processes with partial cellular detachment from basement membrane. Edema of alveolar wall and interstitium were concomitantly occured with endothelial injury. Both type I and type II pneumocytes were injured at late phase,
characterized
by
intracytoplasmic edema, dilatation of ER and irregular cytoplasmic processes in type I pneumocytes and depletion of intracytoplasmic osmiophilic bodies in type II pneumocytes. In the alveolar spaces, accumulation of necrotic cell debris and
exuate
was
noted. Above changes wee progressed until 24 hours after endotoxin injection.
The nitrogen mustard-treated animals revealed neutrophilis sequestration into lumina of alveolar capillaries at 1 hour after endotoxin, but the degree of swelling or formation of irregular cytoplasmic processes of endothelial cells was milder as
well as
the interstitial edema is reduced. The edema of laveolar wall and endothelial injuries were not progressed.
The splenectomized animals revealed marked inflammatory cellular sequestration into alveolar capillary lumina with endotheial cellular injury, Interstitial edema and thickening or alveolar wall were also noted. Accumulation of inflammatory cells
and
exudate was noted in the alveolar spaces.
According to the permeabillity study using the HRP, HRP reaction postive particles were found in the basement membrane and interstitium at 1 hour after endotoxin injeciton. The distribution of HRP positive particles was progressively extended
with
time.
In the condition of neutrophil depletion, the rate of spreading and distribution of HRP reaction positive particles was reduced.
These results suggested that neutrophils may be one of the important factors involving endotoxin induced lung injury, Depletion of neutrophil could reduce the endotoxin induced pulmonary dedma, in another word, may prevent the progression of
ARDS.
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