Humoral First-Line Mucosal Innate Defence in vivo

Abstract

Based on observations in vivo in guinea-pig and human airways, this review presents plasma exudation as non-sieved transmission of bulk plasma across an unperturbed mucosa that maintains its normal barrier functions. Several steps have led to the present understanding of plasma exudation as a non-injurious response to mucosal challenges. The implication of a swift appearance of all circulating multipotent protein systems (also including antimicrobial peptides that now are viewed as being exclusively produced by local cells) on challenged, but intact, mucosal surfaces cannot be trivial. Yet, involvement of early plasma exudation responses in innate mucosal immunology has dwelled below the radar. Admittedly, exploration of physiological plasma exudation mechanisms requires in vivo approaches beyond mouse studies. Plasma exudation also lacks the specificity that is a hallmark of biological revelations. These aspects separate plasma exudation from mainstream progress in immunology. The whole idea, presented here, thus competes with strong paradigms currently entertained in the accepted research front. The present focus on humoral innate immunity in vivo further deviates from most discussions, which concern cell-mediated innate defence. Indeed, plasma exudation has emerged as sole in vivo source of major mucosal defence proteins that now are viewed as local cell produce. In conclusion, this review highlights opportunities for complex actions and interactions provided by non-sieved plasma proteins/peptides on the surface of intact mucosal barriers in vivo.

Early humoral defence: Contributing to confining COVID‐19 to conducting airways?

“…This and other aspects of airway plasma exudation mechanisms have previously been updated in separate reviews that, based on in vivo data, challenge several paradigms in airway research. [11][12][13] In this review, key original observations are listed under appropriate headings. The general idea is that basic physiological co-operation between airway microcirculation and the juxtapositional pseudostratified epithelial lining (Figure 1) are designed to provide potent opportunities for early innate immune responses to environmental challenges.…”

“…Its wellcontrolled duration at the endothelial level, the extravasation being self-abortive unless challenges increase, is also important. 11,13 Following mucosal challenge-induced extravasation of plasma in nasal and tracheobronchial airways, the plasmaderived macromolecules are swiftly transmitted across the intact, pseudostratified epithelial lining in humans and guinea pigs. Crucially, the epithelial passage occurs without altering the normal barrier function of the mucosa.…”

“…Crucially, the epithelial passage occurs without altering the normal barrier function of the mucosa. 12,13 Airway mucosal challenges with microbes, autacoids and allergens cause localized and actively controlled extravasation of bulk plasma. This occurs between transiently separated endothelial cells in post-capillary venules belonging to the airway subepithelial microcirculation.…”

“…31 Considering its non-sieved nature, 12 plasma exudation in human airways would be best reflected by large proteins such as fibrinogen and alpha2-macroglobulin. 12,13 Exudation of alpha2-macroglobulin suggests an opportunity for the entire plasma cascade systems to defend on challenged, yet intact, mucosal surfaces 12 (Figure 1).…”

A Leak in the Dike

“…These include chemokine production to recruit immune cells, synthesis of antibacterial molecules, and interaction with the adaptive immune system during immunization [1][2][3][4]. In this issue, Carl Persson [5] takes a thought-provoking and maybe unorthodox viewpoint on host defense at the mucosal surfaces in his review. He discusses the importance of non-sieved plasma proteins/ peptides at the surface of intact mucosal barriers in vivo.…”