Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes

Abstract

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 gg kg-') 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-', i.p., 16-18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 jig kg-') and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 gg kg-') 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-', i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 fig kg-') on the airways, however the effects of the higher dose of PAF (5.0 ig kg-') 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 gg kg-') and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 gig kg-') on the permeability of the trachea, upper and lower bronchi respectively. 6 The combined injection of the TxA2-mimetic (U-44069; 5.0 gig kg-') and PAF (1.0 and 5.0 gig kg-') 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-') and 5-hydroxytryptamine (methysergide; 2.5 mg kg-') did not cause a significant inhibition of the effect of PAF (1.0 and 5.0 gig kg-') 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.

Role of T cells, cytokines and antibody in dengue fever and dengue haemorrhagic fever

“…Numerous cytokines and mediators have been shown, or suggested, to be able to induce endothelial permeability, these include IL-1 and IL-1 [85], IL-2 [86], IL-6 [87], IL-8 [82] TNF- [88], IFN- [89], histamine [90], platelet activating factor (PAF) [91] and vascular endothelial growth factor (VEGF) [92,93]. As discussed above, many of these, including TNF-, IL-2, IL-6, IL-8 and IFN-, have either been shown to be elevated during dengue infection or released by cells infected with dengue [19,57,61,74,77].…”

The inositol trisphosphate pathway mediates platelet-activating-factor-induced pulmonary oedema

“…In vivo, besides bronchoconstriction [22], PAF produces many effects that may contribute to oedema formation, for example, hydrostatic mechanisms, such as activation of neutrophils [23,24], pulmonary vasoconstriction [25,26] and platelet aggregation [24]. Although these factors may aggravate pulmonary oedema, the major factor in PAF-induced oedema formation appears to be increased vascular permeability.…”

Effect of Y-24180, a Long-Acting Antagonist to Platelet-Activating Factor (PAF), on PAF-lnduced Reactions: A Relationship between the Partial Structure of the Compound and Its Duration of the Action

“…Thus, PAF is involved in the pathogenesis of allergic and inflammatory reactions [1]. Especially, PAF relates closely to the pathogenesis of asthma because this mediator causes airway hyperresponsiveness [2][3][4][5], acute bronchoconstriction [6-9], airway microvascular leak age [10][11][12][13], chemotaxis of eosinophils into the lung [14][15][16][17], and so on. These symptoms are prominent pathological features of asthma [18].…”