Plasma exudation as a first line respiratory mucosal defence

Abstract

A great variety of provocations of the airway mucosa produce extravasation of plasma from the abundant subepithelial microvessels. A plasma exudate has important actions through its volume, its specific and unspecific binding proteins, its enzyme systems, and its potent peptides (of kinin, complement, coagulation, fibrinolysis and other systems). If allowed to operate on the surface of an intact mucosa the plasma exudate would have important roles in normal airway defence. Recent observations in guinea-pig tracheobronchial airways and in human nasal airways suggest that the mucosal exudation of plasma into the airway lumen is a non-injurious fully reversible process. Threshold exudative responses thus resulted in the appearance of an 'unfiltered' plasma exudate not only in the lamina propria but also on the surface of an undisrupted mucosa. Even after extensive luminal entry of exudate the epithelial lining was intact, as judged by light, fluorescence and electron microscopy. Hence, the epithelial barrier was reversibly permeable when approached from beneath by the plasma exudate. This was a distinct increase in outward permeability, because even during the exudation of plasma the mucosa remained a barrier to luminal solutes. It is possible that the exudate itself, by a slight compressive action on the basolateral aspect of epithelial cells, creates intercellular pathways for its entry into the lumen. Contrary to current beliefs, we propose that plasma exudation should be considered a first line respiratory defence mechanism operating together with other systems of the mucosal surface.

Haemophilus influenzae Surface Fibrils Contribute to Serum Resistance by Interacting with Vitronectin

“…Binding of complement inhibitors such as vitronectin, C4BP, or factor H is an efficient strategy used by serumresistant pathogens (30 -32). Several studies have indicated that complement proteins and regulators are present in the human respiratory tract (33,34). Moreover, complement activity can be detected in the ECM during inflammation (34,35).…”

Contribution of Plasma‐Derived Molecules to Mucosal Immune Defence, Disease and Repair in the Airways

“…Indeed, the exudation process itself has been thought to cause epithelial damage and disruption. However, this notion is inconsistent with the actual in vivo data demonstrating that bulk movement of plasma proteins to the airway lumen neither causes, nor is a reliable sign of, mucosal damage [7,8]. Acute luminal entry of bulk plasma can thus occur without disturbing the integrity of the epithelium as a tight absorption barrier in animal and human airways.…”

“…Furthermore, luminal entry of bulk plasma may be extensive, even in airways that maintain their epithelial absorption barrier uncompromised and that exhibit no sign of tissue oedema [7,8]. These new data imply that plasma exudative responses may readily contribute to the first-line respiratory defence system [7]. In addition, it is conceivable that a dynamic mixture of plasmaderived molecules contributes significantly to the biology of the airway mucosa that is activated, but not necessarily injured, by inflammatory mediators.…”

Haemophilus influenzae Interacts with the Human Complement Inhibitor Factor H

“…The binding of C4BP by C. albicans has been shown to mediate adherence to endothelial cells, and bound FHL-1 to S. pyogenes mediates and enhances the ingestion of the pathogen into epithelial cells (54,57). In fact, several studies have indicated that complement proteins and regulators are present in the respiratory tract (50,60,61). Whether FH and/or FHL-1 has any role in adhesion of Hib to epithelium remains to be studied.…”