EFFECT OF PAF ON RAT LUNG VASCULAR-PERMEABILITY - ROLE OF PLATELETS AND POLYMORPHONUCLEAR LEUKOCYTES

1 The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A2 (TxA2), 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 mug 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 mug kg-1) and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 mug 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 mug kg-1) on the airways, however the effects of the higher dose of PAF (5.0 mug 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 mug kg-1) and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 mug kg-1) on the permeability of the trachea, upper and lower bronchi respectively. 6 The combined injection of the TxA2-mimetic (U-44069; 5.0 Ag kg-1) and PAF (1.0 and 5.0 mug 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 mug 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, TxA2 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.