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Institute of Vascular Medicine, The Third Hospital, Beijing Medical University, Beijing, People’s Republic of China
Our previous data have shown that rat lymphocytes can synthesize calcitonin gene-related peptide (CGRP), a neuropeptide. In this study the type, characteristics, and functional role of lymphocyte-derived CGRP were investigated. The results showed that treatment with Con A (4 µg/ml) and recombinant human IL-2 (rhIL-2; 750 U/ml) for 3–5 days induced CGRP synthesis and secretion by lymphocytes from both thymus and mesenteric lymph nodes in a time-dependent manner. Stimulation of these cells with Con A (1–8 µg/ml) or rhIL-2 (94–1500 U/ml) for 5 days induced a significant increase in CGRP secretion in a concentration-dependent manner. The maximal secretion of CGRP with Con A by thymocytes was elevated from 104 ± 11 to 381 ± 44 pg/108 cells, and that by mesenteric lymph node lymphocytes was elevated from 83 ± 10 to 349 ± 25 pg/108 cells, respectively. The maximal CGRP secretion with rhIL-2 by thymocytes was elevated from 116 ± 3 to 607 ± 23 pg/108, and that by mesenteric lymph node lymphocytes was elevated from 117 ± 9 to 704 ± 37 pg/108 cells, respectively. The nucleotide sequencing study showed that lymphoid cells expressed ß-CGRP cDNA only. The levels of ß-CGRP mRNA in mitogen-stimulated lymphocytes of both sources were also increased. However, LPS had no such effect on either source of cells. hCGRP8–37 (2.0 µM), a CGRP1 receptor antagonist, enhanced Con A-induced proliferation and IL-2 release of thymocytes by 41.3 and 35.8% over those induced by Con A alone, respectively. The data suggest that T lymphocyte mitogens can induce the production of endogenous ß-CGRP from T lymphocytes, which may partially inhibit the proliferation and IL-2 release of rat T lymphocyte under immune challenges.
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