Distribution of Substance P-Immunoreactive and Calcitonin Gene-Related Peptide-Immunoreactive Nerves in Normal Human Lungs

Abstract

The distribution of substance P (SP)-immunoreactive (IR) and calcitonin gene-related peptide (CGRP)-IR nerves in normal human lungs was immunohistochemically investigated. SP-IR and CGRP-IR nerves were found in lamina propria and adjacent to blood vessels, and also in some of the ganglia and nerve bundles in the submucosal area. Comparison of serial consecutive sections revealed that SP-IR and CGRP-IR nerves represented similar distribution patterns. CGRP-IR nerves were scarce in bronchial smooth muscles, whereas SP-IR nerves were always present therein. Neither SP-IR nor CGRP-IR nerves were found, however, among submucosal glands or in alveolar septa. These localization patterns were closely related to the functions of SP and CGRP in normal lungs.

Tissue Optical Clearing, Three-Dimensional Imaging, and Computer Morphometry in Whole Mouse Lungs and Human Airways

“…We also pushed the limit of our technique by quantifying a rarer subset (15% total ganglia) that expresses substance P, which is implicated in lung disease and airway hyperresponsiveness (38,39). This low sampling probability of substance P may explain contradictory findings of the presence of substance P in human intrinsic ganglia (36,37). Our initial data about all intrinsic ganglia agrees with previous studies reporting that deeper (adventitial) ganglia contained more cell bodies than shallower (submucosal) ganglia (22).…”

“…We obtained the first images of full-thickness trachea innervation and modeled full-thickness tissue compartments with complex 3D morphology. This allowed us to easily quantify a very sparsely and unevenly distributed set of structures-the instrinsic airway ganglia-which in previous studies required laborious tissue sampling (22,(36)(37)(38). We also pushed the limit of our technique by quantifying a rarer subset (15% total ganglia) that expresses substance P, which is implicated in lung disease and airway hyperresponsiveness (38,39).…”

Neurogenic mechanisms in bronchial inflammatory diseases

“…While substance P is principally activating the NK1 receptors, neurokinin A mainly acts via NK2 and neurokinin B via NK3 receptors (40)(41)(42). A differential pattern of tachykinin receptor distribution is present in the respiratory tract: While NK1 receptors are predominantly localized to the airway epithelium, submucosal glands, and vessels, NK2 receptors are mainly expressed on the airway smooth muscle (43)(44)(45).…”

Characterization of the tachykinin NK2 receptor in the human bronchus: influence of amastatin‐sensitive metabolic pathways

“…Tachykinin-containing sensory nerves are present in the human airways (Lundberg et al, 1984;Martling et al, 1987;Komatsu et al, 1991). In human bronchial smooth muscle, natural tachykinins (TKs) (substance P, neurokinin A, neurokinin B) act as potent inducers of mucus secretion (Rogers et al, 1989) and smooth muscle contraction (Advenier et al, 1987;Honda et al, 1991).…”