Three-dimensional mapping of sensory innervation with substance p in porcine bronchial mucosa: comparison with human airways.
In asthma, neurogenic inflammation in bronchial airways may occur though the release of neuropeptides from C fibers via an axon reflex. Structural evidence for this neural pathway was sought in the pig and in humans by three-dimensional mapping of substance P-immunoreactive (SP-IR) nerves in whole mounts of mucosa using immunofluorescent staining and confocal microscopy. To show continuity, nerves were traced with 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate from their epithelial endings through the mucosa. The pan-neuronal marker protein gene product 9.5 revealed an extensive apical and basal plexus of nerves in the epithelium; 94% of these were varicose SP-IR fibers. Apical SP-IR fibers had a length density of 88 mm/mm(2). Varicose apical processes followed closely around the circumference of goblet cells. Calcitonin gene-related peptide was colocalized with SP-IR in varicosites. The epithelial fibers converged into bundles as they entered the lamina propria where lateral branches ran along arterioles, often contiguous with the vascular smooth muscle. 1,1'-didodecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate tracing showed that they projected to the epithelium. SP-IR fibers were rare near postcapillary venules. In human bronchial epithelium, protein gene product 9.5 revealed a similar apical and basal plexus of varicose fibers that weakly stained for SP-IR. Thus, a continuous sensory nerve pathway from the epithelium to arterioles provides structural support for a local axon reflex.
Lamb
Jasmine P
JP
Department of Physiology, University of Western Australia, Nedlands, Western Australia. jlamb@cyllene.uwa.edu.au
Sparrow
Malcolm P
MP
D000328:Adult; D000344:Afferent Pathways / Q000276:immunology / Q000473:pathology; D000368:Aged; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000294:innervation* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000294:innervation* / Q000473:pathology*; D013373:Substance P / Q000494:pharmacology*; D013552:Swine
D013373:Substance P