Quantitative assessment of increased airway microvascular permeability to ¹²⁵I‐labelled plasma fibrinogen induced by platelet activating factor and bradykinin

Abstract

1 We have used 125I-labelled fibrinogen (I-FN) in experiments monitoring plasma extravasation from vessels within guinea-pig trachea and peripheral lung tissue in response to platelet activating factor (PAF) and bradykinin (BK). Retained tissue radioactivity derived from I-FN was detected by direct measurement and by autoradiography. 2 Both PAF and BK caused concentration-dependent increases in radioactivity in trachea and peripheral lung, with PAF being approximately 1000 times more potent than BK at both sites. On a wet weight basis, mean tracheal leakage responses to PAF and BK were approximately 6 times and 2 times greater respectively than those in peripheral lung. Furthermore, in trachea, the maximal response to PAF was nearly twice that to BK, although they were approximately equiactive in peripheral lung. Autoradiograms showed that both agonists caused increases in peripheral bronchial circulation microvascular permeability to I-FN. No evidence for leakage in alveolar wall capillaries or in pulmonary blood vessels was observed. Quantitation of such autoradiographic data will allow a comprehensive evaluation of the effects of putative asthma mediators on microvascular permeability throughout the respiratory tree.

Mechanisms of fibrinogen‐induced microvascular dysfunction during cardiovascular disease

“…In addition, leakage of Fg itself through the EC layer was also increased if its content was elevated (Tyagi et al. 2008), confirming the possibility that Fg leakage through the vascular wall was induced by different agonists (Pedersen et al. 1991) or even diseases (Areekul 1986).…”

Mechanisms of Increased Airway Microvascular Permeability: Role in Airway Inflammation and Obstruction

“…Dose-dependent plasma extravasation involved vessels within both central and peripheral airways (Pedersen et al 1991 …”

“…Intravenous PAF is approximately 1000 times more potent than histamine or BK and 10 times more potent than LTD4, as an inducer of plasma extravasation (Evans et al 1989;Pedersen et al 1991;Tokuyama et al 1991~). Dose-dependent plasma extravasation involved vessels within both central and peripheral airways (Pedersen et al 1991…”

“…Agents which might be used to control airway microvascular leakage include antagonists of specific receptors for mediators of microvascular leakage, such as PAF (Evans et al 1988a), histamine (Evans et al 1989;Goldie et al 1990), L T G and LTD4 (Goldie et al 1990), BK (Pedersen et al 1991;Sakamoto et al 1992), S P (Sakamoto et al 1993) and NK-A (Tousignant er al. 1993).…”

“…1991). In the guinea-pig, the effect of BK on microvascular permeability is mediated via BK B2-receptors(Pedersen et al 1991;Sakamoto et al 1992Sakamoto et al , 1993, in part involving the neuronal release of peptides such as substance P (SP; Sakamoto et al1993). As is the case for PAF and LT, a…”