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Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes
Author(s) -
Sirois Martin G.,
Lima Wothan Tavares,
Fernandes Artur José de Brum,
Johnson Richard J.,
Plante Gérard E.,
Sirois Pierre
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14859.x
Subject(s) - platelet , vascular permeability , lung , chemistry , immunology , medicine
1 The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A 2 (TxA 2 ), histamine and 5‐hydroxytryptamine to platelet activating factor (PAF)‐mediated protein extravasation in rat lungs. 2 Intravenous injection of PAF (1.0 and 5.0 μg kg −1 ) increased dose‐dependently (up to 7.5 fold) the vascular permeability of the trachea, upper and lower bronchi to Evans blue dye (EB), a marker of albumin extravasation. The permeability of the pulmonary parenchyma was not affected significantly by PAF. 3 Thrombocytopenia induced by administration of the IgG fraction of goat anti‐rat platelet serum (APS; 15 mg 100 g −1 , i.p., 16–18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 μg kg −1 ) and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 μg kg −1 ) on the permeability of the trachea, upper and lower bronchi respectively to albumin. 4 PMNL depletion induced by administration of rabbit anti‐rat polymorphonuclear serum (ANS; 2 mg kg −1 , i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 μg kg −1 ) on the airways, however the effects of the higher dose of PAF (5.0 μg kg −1 ) on the permeability of the trachea, upper and lower bronchi to albumin were reduced by 43, 25 and 23% respectively. 5 The injection of both the anti‐platelet and the anti‐PMNL sera reduced by 61, 62 and 96% the effects of the lower dose of PAF (1.0 μg kg −1 ) and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 μg kg −1 ) on the permeability of the trachea, upper and lower bronchi respectively. 6 The combined injection of the TxA 2 ‐mimetic (U‐44069; 5.0 μg kg −1 ) and PAF (1.0 and 5.0 μg kg −1 ) in thrombocytopenic rats overcame the vascular permeability decrease induced by APS treatment. 7 Pretreatment of the animals with a combination of antagonists to histamine (mepyramine; 3.0 mg kg −1 ) and 5‐hydroxytryptamine (methysergide; 2.5 mg kg −1 ) did not cause a significant inhibition of the effect of PAF (1.0 and 5.0 μg kg −1 ) on EB extravasation in the airways. 8 These data show that the effect of intravenous PAF on rat vascular permeability is partly modulated by polymorphonuclear leucocyte and platelet activation. Our results suggest that following its release, TxA 2 could increase postcapillary hydrostatic pressure by inducing a venoconstriction and potentiate the extravasation elicited by PAF. These results do not suggest a major role for histamine and/or 5‐hydroxytryptamine on PAF‐induced albumin extravasation.