Neuropeptide Regulation of Human Thymocyte, Guinea Pig T Lymphocyte and Rat B Lymphocyte Mitogenesis

Abstract

The effect of 15 defined neuropeptides on the mitogenic activation of lymphocytes from human thymus, guinea pig lymph nodes and rat spleen was investigated. Lymphocytes were incubated in the absence or presence of polyclonal T and B cell activators together with increasing doses of the neuropeptides, and harvested at 48 h of culture after pulse-labeling with ³H-thymidine to assess the DNA synthesis. A dose-related stimulatory effect on the spontaneous ³H-thymidine incorporation of human thymocytes was obtained with methionine-enkephalin (met-enk), motilin and neurotensin. Vasoactive intestinal polypeptide (VIP) and peptide HI (PHI) were inhibitory. A similar responsiveness was observed in cultures of phytohemagglutinin P (PHA)-activated human thymocytes. The low level of basal DNA synthesis of guinea pig lymph node cells was stimulated by VIP and inhibited by neuropeptide Y (NPY) and PHI. PHA-activated lymph node T lymphocytes were stimulated by neurotensin, bombesin and motilin, whereas NPY inhibited the thymidine uptake. The low rate of spontaneous DNA synthesis of rat spleen cells was increased in the presence of VIP. Met-enk stimulated both basal and dextran sulfate-activated splenic B cell proliferation, whereas PHI was inhibitory in both cases. The following peptides were found to be inactive in all the above assays: substance P, cholecystokinin-octapeptide, somatostatin, galanin, oxytocin, pentagastrin and gastrin-releasing peptide 1–27 and 14–27. Although the responses were generally of low magnitude and observed at high peptide concentrations, the present study contributes to the understanding of possible mechanisms involved in interactions between the nervous and the immune system.

The Tachykinins Neurokinin A and Physalaemin Stimulate Murine Thymocyte Proliferation

“…One reason for these conflicting results could be that we have used splenic T cells from a rodent source, whereas Payan et al [1983] used human pe ripheral blood T lymphocytes in their study. Our negative findings with SP are, however, supported by previous results [Söder and Hellström, 1987] and by findings of Nordlind and Mutt[1986a, b].…”

“…Neuropeptides are known to influence lympho cyte proliferation [Ottaway and Greenberg, 1984;Nordlind and Mutt, 1986a, b;Sandberg and Ljungdahl, 1986;Söder and Hellström, 1987;Nordlind, 1988] and effector functions [Mathews et al, 1983;Payan and Goetze, 1985], as well as macrophage acti vation [Bar-Shavit et al, 1982], The tachykinin family represents a group of biologically active neuropep tides with C-terminal amino acid sequence homology [Erspamer, 1981] and a wide distribution in the cen tral, peripheral and enteric nervous systems [Costa et al, 1980;Furness et al, 1982]. In the periphery, they are demonstrated in primary C fibres of sensory neu rons [Hökfelt et al, 1975;Otsuka et al, 1975] and, upon release, considered to act as potent inducers of neurogenic inflammatory reactions [Pernow, 1983[Pernow, , 1985a, Tachykinins occur abundantly in inflamed tissues such as arthritic joints [Lotz et al, 1988;Marx, 1988], and in tissues serving as primary barriers of the host defence against microbial invasion [Stanisz and Bienenstock, 1988].…”

Motilin stimulates preadipocyte proliferation and differentiation and adipocyte lipid storage

“…Our present results are the first to show that motilin can stimulate both cell proliferation and mitochondrial activity in 3T3-L1 preadipocytes. Proliferative effects of motilin had been observed previously in pig T lymphocytes (35) but not in rabbit enteric smooth muscle cells (44). The results obtained here are the first to provide evidence for increased 3T3-L1 preadipocyte production of formazan, suggesting that motilin could stimulate cell mitochondrial activity through the activation of mitochondrial functions.…”

Vasoactive Intestinal Peptide in Thymus: Synthesis, Receptors and Biological Actions

“…One of the initial observations about the effect of VIP in the immune system was the inhibition of T-cell proliferation in response to mitogen stimulation. In this respect, VIP inhibits in a dose-dependent manner the mitogenesis of human and murine thymocytes stimulated with phytohemagglutinin and through the TCR/CD3 complex [67,75,76], suggesting a role in the differentiation, activation, and/or proliferation of T cells. In a recent study, we have described that VIP protects thymocytes from glucocorticoid-induced apoptosis [77].…”