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.

Keywords: Humoral innate immunity; Mucosal barrier; Plasma exudation.

Fig. 1

Topical airway challenges with non-injurious autacoids cause exudation of bulk plasma, which is characterized by a maintained ratio between small (albumin) and large (alpha2-macroglobulin) plasma proteins in airway surface liquids as in the circulation. By this swift, humoral mechanism the entire range of circulating plasma molecules are moved to the surface of an intact mucosa. Mucosal oedema is not induced and, despite letting through non-sieved plasma macromolecules, the barrier function of the airway mucosa against inhaled molecules is not reduced. Reflecting the asymmetry and plasticity of epithelial barrier cells, a slight increase in basolateral hydrostatic pressure produces such unidirectional paraepithelial perviousness. Plasma-derived molecules thus have ample opportunities to participate in first line innate defence of the intact mucosa in vivo.