Gj. Phillips et al., OXYGEN-INDUCED LUNG INJURY IN THE PRETERM GUINEA-PIG - THE ROLE OF LEUKOTRIENE B-4, Respiratory medicine, 89(9), 1995, pp. 607-613
Citations number
28
Categorie Soggetti
Cardiac & Cardiovascular System","Respiratory System
Leukotriene B-4 (LTB(4)) has been reported to promote the formation of
lung oedema when infused into the pulmonary circulation of adult anim
als. The present study evaluated the hypothesis that LTB(4) was respon
sible, in part, for the oedema that develops during oxidative injury o
f the immature lung. Significant increases were found in LTB(4) concen
tration in bronchoalveolar lavage fluid obtained from pre-term guinea
pig pups maintained in 95% oxygen for 48 h (P<0.05) and 72 h (P<0.05)
compared to pups maintained in 21% oxygen. Cellular analysis of lavage
fluid revealed a concurrent influx of neutrophils into the hyperoxic-
injured lung at these times. The protein concentration of lavage fluid
was also increased by 48-h hyperoxia exposure indicating elevated pul
monary microvascular permeability. In a second series of experiments,
pups exposed to 95% oxygen (and 21% oxygen controls) were treated with
a specific LTB(4) antagonist (U-75302), at either 0.5, 1.5 or 3.0 mg
100 g body wt to ascertain if LTB(4) played a role in either neutrophi
l recruitment or oedema formation in the immature lung. The number of
neutrophils recovered in bronchoalveolar lavage fluid was significantl
y reduced, compared to vehicle-treated pups, in pups treated with U-75
302, at both 1.5 and 3.0 mg/100 g body wt but not 0.5 mg/100 g body wt
. Histopathological analysis of pups treated with 1.5 mg U-75302/100 g
body wt revealed fewer neutrophils in the pulmonary interstitium (198
vs. 218 mm(-2), P<0.05). The extent of lung microvascular permeabilit
y, elevated by hyperoxic exposure, was modulated by increasing concent
rations of U-75302. Specifically, treatment with 0.5, 1.5 and 3.0 mg U
-75302/100 g body wt reduced microvascular permeability by 17, 67 and
98%, respectively. In conclusion, LTB(4) plays an important role in oe
dema formation in acute oxidative injury of the immature lung and this
is mediated, in part, through neutrophils.