Present results provide evidence for the localization of gp140-trkA-like IR in: (1) nerve cells which are known to be NGF-responsive, and (2) non-nervous cutaneous tissues which are innervated by NGF-dependent peripheral neurons. These findings suggest that, in addition to the well-established role of NGF on sensory and sympathetic neurons, this neurotrophin may be able to regulate some other functions on non-nervous cells which are targets for NGF-dependent peripheral neurons.

We used immunohistochemical techniques and monoclonal antibodies to localize two basement membrane components (laminin and type IV collagen) in the nerves and sensory nerve formations, or corpuscles, supplying human digital skin. Furthermore, neurofilament proteins, S-100 protein and epithelial membrane antigen were studied in parallel. In dermal nerve trunks, immunostaining for laminin and type IV collagen was found to be co-localized in the perineurium and the Schwann cells, the stronger immunoreactivity being at the external surface of the cells. In the Meissner digital corpuscles, the immunoreactivity for laminin and type IV collagen was mainly observed underlying the cell surface of lamellar cells, while the cytoplasm was weakly immunolabelled or unlabelled. Finally, within Pacinian corpuscles co-localization of the two basement membrane molecules was encountered in the inner core, intermediate layer, outer core and capsule. Laminin and type IV collagen immunoreactivities were also found in blood vessels and sweat glands, apparently labelling basement membrane structures. The present results provide evidence for the presence of basement membrane in all periaxonic cells forming human cutaneous sensory nerve formations, and suggest that all of them are able to synthesize and release some basement membrane components, such as laminin and type IV collagen. The possible role of laminin in sensory nerve formations is discussed.

The nerve growth factor (NGF) receptors p75LNGR and TrkA are expressed by thymic epithelial cells. Presumably, the NGF-TrkA system is involved in the paracrine communication between thymic epithelial cells and thymocytes, whereas the functional role of p75LNGR is still unknown. The thymus of vertebrates undergoes age-related changes that in part depend on hormonal factors. In order to find out whether thymic epithelial cells are responsive to NGF during the whole lifespan of the rat, we studied NGF receptor expression in the thymus from birth to 2 years of age, using immunohistochemistry. Furthermore, to evaluate whether increased plasma levels of NGF affected the ageing process, either NGF or 4-methylcatechol (4MC), an inductor of NGF synthesis, was administered. Both TrkA and p75LNGR were expressed by a subpopulation of thymic epithelial cells during the whole age range studied and their expression peaked at around 3 months. TrkA was primarily found in subcortical and medullary epithelial cells, whereas p75LNGR was seen in a subpopulation of medullary cells. Cortical epithelial cells, neural crest-derived cells, other stromal cells and thymocytes were not immunoreactive for NGF receptors. Neither the administration of NGF nor the increased NGF plasma levels obtained after 4MC treatment seemed to affect the ageing of the thymus as assessed by morphological and immunohistochemical criteria, but this increase in NGF levels did produce a shift in the expression of p75LNGR from epithelial cells to ED1-positive macrophages in animals of 6 months and older. Present results indicate that the expression of p75LNGR and TrkA in the rat thymus undergoes age-dependent changes that parallel those of epithelial cells. NGF could therefore be important for thymus homeostasis, possibly acting on epithelial cells. Nevertheless, NGF did not seem to be able to prevent the involution of this organ, although it produced a switch in the expression of p75LNGR, the significance of which remains to be established.

No abstract

These results suggest that TrkA ligands may be involved in the control of thymic epithelial cells. This could be of potential importance because of the involvement of these cells in providing an appropriate microenvironment for maturation and selection of T lymphocytes.