Airways exudation of plasma macromolecules: in innate defense, epithelial regeneration, and asthma

Publication date: Available online 29 August 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Carl Persson;

Abstract

This review discusses in vivo airway aspects of plasma exudation in relation to current views on epithelial permeability and epithelial regeneration in health and disease. Microvascular-epithelial exudation of bulk plasma proteins characteristically occurs in asthma being especially pronounced in severe and exacerbating asthma. Healthy human and guinea-pig airways challenged by non-injurious histamine-leukotriene-type autacoids also respond by prompt mucosal exudation of non-sieved plasma macromolecules. Contrary to current beliefs, epithelial permeability in the opposite direction (=absorption of inhaled molecules) has not been increased in asthma and allergic rhinitis or in acutely exuding healthy airways. A slightly increased subepithelial hydrostatic pressure produces such unidirectional outward perviousness to macromolecules. Lack of increased absorption permeability in asthma may further be reconciled with occurrence of epithelial shedding leaving small patches of denuded basement membrane. Counteracting escalating barrier breaks, plasma exudation promptly covers the denuded patches. Here it creates, and sustains, a biologically active barrier involving a neutrophil-rich, fibrin-fibronectin net. Further, in the plasma-derived milieu all epithelial cell types bordering the denuded patch dedifferentiate and migrate from all sides to cover the denuded basement membrane. However, the speedy epithelial regeneration may come at a cost. Guinea-pig in vivo-studies demonstrate that patches of epithelial denudation-regeneration are exudation hot spots evoking asthma-like features including recruitment/activation of granulocytes, proliferation of fibrocyte/smooth muscle cells, and basement membrane thickening. In conclusion, non-sieved plasma macromolecules can operate on the intact airway mucosa as potent components of first line innate immunity responses. Exuded plasma also takes center stage in epithelial regeneration. When exaggerated, epithelial regeneration may contribute to inception and development of asthma.

https://ift.tt/2wqCOC3