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Three-Dimensional Mapping of Sensory Innervation with Substance P in Porcine Bronchial Mucosa

Comparison with Human Airways

Department of Physiology; and The Asthma Institute of Asthma and Allergy, Department of Medicine, University of Western Australia, Nedlands, Western Australia

Correspondence and requests for reprints should be addressed to Jasmine P. Lamb, Department of Physiology, University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia 6009. E-mail: jlamb{at}cyllene.uwa.edu.au

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/mm². 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.

Key Words: neurogenic inflammation • substance P • afferent pathways • bronchi/innervation • human/physiology • swine/physiology • neuropeptides

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