Production and secretion of calcitonin gene-related peptide from human lymphocytes

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide, which is mainly present in primary sensory nerves. Although our previous study has shown that rat lymphocytes can synthesize beta-CGRP, there is no evidence demonstrating whether CGRP can be synthesized by human lymphocytes. In this study, the production of CGRP from human lymphocytes from spleen and blood were investigated by using CGRP-specific radioimmunoassay (RIA), and RNase protection assay (RPA). The results showed that human T lymphocyte mitogen, such as phytohemagglutinin (PHA), could time- and dose-dependently induce hCGRP secretion; rhIL-2 alone did not effect hCGRP secretion, but it could potentiate PHA-evoked hCGRP secretion from human spleen lymphocytes. RPA showed that alpha- and beta-CGRP mRNA were both constitutively expressed in unstimulated human peripheral blood mononuclear cells (PBMC). PHA could cause beta-hCGRP but not alpha-hCGRP mRNA increase in a time-dependent manner. In addition, hCGRP(8-37), a CGRP(1) receptor antagonist, enhanced PHA or human interleukin-2 (rhIL-2), induced the proliferation of splenocytes and PBMC. These results suggest that hCGRP is produced and secreted by human lymphocyte. Lymphocyte mitogen can induce the elevation of beta-CGRP synthesis and secretion. The lymphocyte-derived beta-CGRP may inhibit, at least in part, lymphocytes proliferation, which are then involved in the modulation of human T lymphocyte function in response to immune stimulation.