The presence and distribution of the presumed pan-neural marker protein gene product 9.5 (PGP)- and peptide-immunoreactive (ir) nerve fibers in alveolar walls of various species was investigated by light microscopic single and double staining immunohistochemistry. PGP-, tachykinin (TK)-, and calcitonin gene-related peptide (CRGP)-ir fibers were sparsely distributed in a similar pattern in alveolar walls of all species investigated. No vasoactive intestinal peptide-, peptide histidine isoleucine-, galanin-, and opioid-ir nerve fibers could be detected. PGP-ir fibers outnumbered those staining for TKs and CGRP. There was partial coexistence of PGP and TK as well as of TK and CRGP. PGP-, TK-, and CGRP-ir fibers were in close spatial relationships to the cells building up the alveolar walls and to alveolar capillaries. The function of PGP is unknown. TK- and CGRP-ir nerves in alveolar walls may be sensory and function as chemo-, stretch-, and/or immuno-receptors. TKs and CGRP released from alveolar fibers may influence the alveolar epithelium and the various non-epithelial alveolar cells, including immune cells. The alveolar TK and CGRP innervation may be of unrecognized importance in physiological and pathophysiological regulation of lung functions.
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