Interrelation of peptidergic innervation with mast cells and ED1-positive cells in rat thymus

The peptidergic innervation of rat thymus has been investigated by immunohistochemical methods, focusing on the spatial interrelationship of peptidergic nerve fibers with mast cells and macrophages in the rat. An antiserum directed against the protein gene product 9.5 (PGP 9.5) regarded as a pan-neuronal marker revealed a rich innervation, especially in the subcapsular cortex, in interlobular septa, and of the vasculature in the cortex and the corticomedullary boundary. A minor proportion of PGP 9.5-immunoreactive (ir) fibers supplied the thymic parenchyma. The main component of peptidergic innervation consisted of fibers costaining for tachykinins (TKs) and calcitonin gene-related peptide (CGRP), but considerable amounts of neuropeptide Y (NPY)/tyrosine hydroxylase (TH)-positive fibers and vasoactive intestinal polypeptide/peptide histidine isoleucine-positive fibers also were present. There were sparse Leu-enkephalin and galanin immunoreactivities in thymic nerve fibers, while neurotensin was absent from nerve fibers. Close associations of TK/CGRP-ir and NPY-ir fibers with mast cells were frequently detected in the connective tissue areas of the thymus, often adjacent to the vasculature. TK/CGRP-ir fibers and some rare NPY-ir fibers were found adjacent to EDl-positive macrophages and less frequently to mast cells. TK/CGRP-ir and NPY-ir fibers were mainly detected in relation to the vasculature of the cortex and the corticomedullary boundary, but also were found in capsular and subcapsular regions of the thymic cortex. The possible importance of the close spatial relationship between the various peptide-containing nerve fibers and mast cells and ED1-positive macrophages in neuroimmune integration is discussed.