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Platelet Activating Factor Receptor (PAFr) Expression Up‐regulation Contributes to Pulmonary Vascular Remodeling in Ovine Fetuses Exposed to Chronic High Altitude Hypoxia
Author(s) -
Bixby Christine,
Ibe Basil,
Abdallah May,
Zhou Weilin,
Longo L.D.,
Raj J. Usha
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a401-b
Subject(s) - platelet activating factor , platelet activating factor receptor , fetus , lung , pulmonary hypertension , downregulation and upregulation , hypoxia (environmental) , receptor , medicine , endocrinology , pathogenesis , immunohistochemistry , biology , chemistry , andrology , biochemistry , antagonist , oxygen , pregnancy , genetics , organic chemistry , gene
PAF is implicated in pathogenesis of chronic‐hypoxia‐induced pulmonary hypertension in animal models and neonates. In this study, we investigated PAFr expression and binding in lung membranes of HAH fetal lambs and age‐matched controls. Membrane proteins (100 μg/ml) were incubated at 4°C for 24 h with 2.5 mg/ml BSA in 30 mM Tris buffer, pH 7.2 and 3 H‐PAF. Receptor bound PAF was extracted and quantified. In control lungs, at 0.05nM 3 H‐PAF, binding (fmol/mg protein) was 395±38, which increased to 736±32 at 0.3nM 3 H‐PAF. The values in lung membranes of HAH fetuses were 555±46 and 892±43, which were significantly higher than control lungs. For immunohistochemical study of PAFr protein expression, lung tissue slices were fixed and PAFr were localized with PAFr antibody in blood vessels. Immunohistochemical examination revealed greater PAF receptor protein expression in vessel media of HAH lungs compared to controls. We also measured PAF acetylhydrolase (PAF‐Ah) activity in HAH and control lungs. Lung homogenates (100μg/ml) were incubated for 15 min with 1.5 μM 3 H‐PAF at 37°C. PAF‐Ah activity was quantified. PAF‐Ah activity (μmol/mg protein/min) in controls was 0.022 and not different from 0.024 in HAH lamb lungs. Our data show that exposure of fetuses to HAH result in significant upregulation of PAFr protein expression in pulmonary vessels, and increased PAFr binding without alteration in PAF catabolism. These findings suggest that PAF may be involved in the pulmonary vascular remodeling that occurs in these animals and predispose them to PPHN. Grant: HL077819