Platelet-activating factor increases lung vascular permeability to protein

Abstract

We studied the effects of platelet-activating factor (PAF) on pulmonary hemodynamics and microvascular permeability in unanesthetized sheep prepared with lung-lymph fistulas. Since cyclooxygenase metabolites have been implicated in mediating these responses, we also examined the role of the cyclooxygenase pathway. PAF infusion (4 micrograms X kg-1 X h-1 for 3 h) produced a rapid, transient rise in pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), plasma thromboxane B2 concentration (TxB2), and pulmonary lymph flow (Qlym). The lymph-to-plasma protein concentration ratio (L/P) did not change from base line. Pretreatment with the cyclooxygenase inhibitor, sodium meclofenamate, prevented the generation of TxB2 and the hemodynamic changes but did not prevent the increase in Qlym. The estimated protein reflection coefficient decreased from a control value of 0.66 +/- 0.04 to 0.43 +/- 0.06 after PAF infusion. We also studied the effects of PAF on endothelial permeability in vitro by measuring the flux of 125I-albumin across cultured bovine pulmonary artery endothelial cells (EC) grown to confluency on a gelatinized micropore filter and mounted within a modified Boyden chemotaxis chamber. PAF (10(-8) to 10(-4) M) had no direct effect on EC albumin permeability, suggesting that the increase in permeability in sheep was not the direct lytic effect of PAF. In conclusion, PAF produces pulmonary vasoconstriction mediated by cyclooxygenase metabolites. PAF also increases pulmonary vascular permeability to protein that is independent of cyclooxygenase products and is not the result of a direct effect of PAF on the endothelium.

Platelet activating factor modulates peptidoleukotriene effects on the permeability of bovine aortic endothelial cell to albumin

“…Incubation of the cells with PAF at concentrations up to 10-SM failed to alter 125I-albumin clearance rate in this BAEC model. These results are in agreement with the previous reports, which showed that PAF treatment (10 -4 M) did not modify the permeability of bovine pulmonary artery endothelial cells (BPAEC) [4] but induced morphologic changes of the cells at a dose of 1 nM [5]. However, our results are not in agreement with another study which showed that LTC 4 as well as LTD 4 treatment did not modify the BPAEC permeability to 125I-albumin [6].…”

Tiam1 and Rac1 Are Required for Platelet-activating Factor-induced Endothelial Junctional Disassembly and Increase in Vascular Permeability

“…The mechanism of PAF-induced disruption of endothelial barrier structure and function is incompletely understood, although PAF is recognized to mediate increased vascular permeability (33) and is involved in the pathogenesis of many inflammatory diseases (7). In vivo experiments in the cat hind limb (59), human and rat skin (60,61), rat venules (12), rat and mouse cremaster (33,34), hamster cheek pouch (62), and sheep lung (63) show that PAF increases markedly vascular permeability to water and macromolecules. Here we show, using in vivo studies, that the engagement of PAF-R caused (i) focal openings of IEJs mostly in capillaries and postcapillary venules, (ii) widening of IEJs, (iii) formation of lamellipodia and filopodia in the affected IEJs, (iv) a shift of G-to F-actin, and (v) formation of endothelial fenestrations and large intracytoplasmic vacuoles.…”

Mechanism of action of platelet activating factor in the pulmonary circulation: an investigation using a novel isotopic system in rabbit isolated lung

“…In a different species, the guinea-pig, Hamasaki and colleagues (1984) have reported that PAF-induced pulmonary oedema is independent of plate- lets. More recently, studies in sheep and rabbit lungs, have suggested that the PAF-mediated oedema is a result of vasoconstriction and is not due to any effect on microvascular permeability (Bolin et al, 1986;Burhop et al, 1986).…”