Plasma leakage inflammatory mediators

There are several consequences of an increase in the permeability of the blood vessels of the airway mucosa. Plasma leakage could result in mucosal edema and the movement of fluid into the airway lumen, both of which could contribute to airflow obstruction. In addition, plasma-derived inflammatory mediators could form in the mucosa and airway lumen, and extravasated plasma proteins could increase the viscosity of sputum. 

Release of Inflammatory Mediators Associated With Plasma Leakage... 

As discussed in Section 3.3, few histopathological studies of asthma have focused specifically on the microvasculature. Nonetheless, there is evidence that neovascularization is one of the changes in the airways of asthmatics (Kuwano et al., 1991). This observation in potentially important because newly formed blood vessels may be abnormally leaky (Schoefl, 1967) or abnormally responsive to inflammatory mediators (McDonald, 1992). The plasma leakage that occurs in the airway mucosa of asthmatics could result from the heightened response of the mucosal blood vessels to inflammatory mediators. 

Depletion of endogenous glucocorticoids in experimental animals can increase the amount of plasma leakage produced by allergen challenge and other inflammatory stimuli (Boschetto et al., 1992 Ohrui et al., 1992). This observation may be important clinically, because the responsiveness of airway blood vessels to inflammatory mediators could increase after glucocorticoid treatment is stopped. 

Selective 182-adrenergic receptor agonists (ft agonists) are widely used in the treatment of airway diseases such as asthma because of their bronchodilating action. In addition, ft agonists have anti-inflammatory effects, in that they can inhibit the release of inflammatory mediators and can decrease plasma leakage (Svensjo et al., 1977 Tomioka etal., 1981 Erjefalt and Persson, 1986 Barnes,... 

Nedocromil, which is structurally different from cromoglycate, also has multiple anti-inflammatory actions (Barnes, 1993c). For example, nedocromil can decrease allergen-induced plasma leakage in guinea-pig airways (Evans et al., 1988b). This effect probably involves the inhibition of mediator release (Moqbel eta.1., 1988). However, an action on vascular endothelial cells... 

Several reports suggest that peptides released from nerve fibers in the airways can decrease the plasma leakage produced by inflammatory mediators (Raud, 1993). For example, calcitonin gene-related peptide (CGRP), which usually co-exists with substance P in sensory nerve fibers, may have an anti-edema effect in the airways (Raud etal.. 

Endogenous histamine has a modulating role in a variety of inflammatory and immune responses. Upon injury to a tissue, released histamine causes local vasodilation and leakage of plasma-containing mediators of acute inflammation (complement, C-reactive protein) and antibodies. Histamine has an active chemotactic attraction for inflammatory cells (neutrophils, eosinophils, basophils, monocytes, and lymphocytes). Histamine inhibits the release of lysosome contents and several T- and B-lymphocyte functions. Most of these actions are mediated by H2 or H4 receptors. Release of peptides from nerves in response to inflammation is also probably modulated by histamine, in this case acting through presynaptic H3 receptors. 

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