vasoactive-intestinal-peptide and Leukemia--Erythroblastic--Acute

In the present study the effect of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), and secretin on spontaneous cell mediated cytotoxicity of peripheral blood mononuclear cells against tumour target cells was evaluated. VIP stimulated cytotoxicity against CaCo-2 human colon cancer cells, whereas less effect was seen against K-562 erythroleukemia cells. Depletion of CD16+ natural killer cells almost completely abolished cytotoxicity and subsequent VIP incubation did not change residual activity. In contrast to PHM, which hardly influenced cytotoxicity, secretin was found to be more effective especially against K-562 target cells. These observations suggest a modulating role for the neuropeptide VIP in the cellular immune response against tumour cells, especially from the colon, resulting in increased activity of CD16+ natural killer cells. Secretin, seems to be less potent in modulating cellular cytotoxicity. These findings support the concept that gastrointestinal peptides can play a role in the regulation of cellular cytotoxicity against tumor cells.

Topics: Colonic Neoplasms; Cytotoxicity, Immunologic; Humans; Killer Cells, Natural; Leukemia, Erythroblastic, Acute; Leukocytes, Mononuclear; Neuroimmunomodulation; Peptide PHI; Secretin; Stimulation, Chemical; Tumor Cells, Cultured; Vasoactive Intestinal Peptide

Receptor-effector coupling in the adenylate cyclase (AC) system was studied using fusion transfer of rat or monkey frontal cortex membranes to Friend erythroleukemia (Fc) cells. The indigenous AC activity of cortex membranes had previously been inactivated with N-ethylmaleimide. In the fusates, the AC activity could be stimulated through beta-adrenoceptors using noradrenaline (NA), or through specific receptors for vasoactive intestinal polypeptide (VIP), or by fluoride which activates the effector components of the AC-system directly, bypassing receptors. There was a critical stoichiometric relationship between the receptor-stimulated cAMP output and the number of recipient cells of the fusion system, i.e. the total AC capacity as measured by fluoride stimulation. In fusates with rat brain membranes, the beta-adrenoceptor coupling increased as the availability of recipient cells increased; on the other hand, the excess of recipient cells did not change the VIP receptor coupling capacity. In fusates with monkey brain membranes, the situation was the opposite: VIP receptor coupling increased as larger amounts of recipient cells were made available, but the beta-adrenoceptor coupling capacity remained unchanged. The differences in coupling capacities were related to differences in receptor binding with higher beta-adrenoceptor density in rat than in monkey frontal cortex membranes, as opposed to higher VIP receptor density in monkey than in rat frontal cortex membranes. Neuropeptide tyrosine (NPY) attenuated both NA- and VIP-induced activation of AC in the fusates; it was equally potent against both agents. In rat brain membrane fusates, the NA-induced AC activity was attenuated in a dose-dependent and apparently non-competitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenylyl Cyclases; Animals; Cell Fusion; Cell Line; Female; Fluorides; Friend murine leukemia virus; Frontal Lobe; Leukemia, Erythroblastic, Acute; Macaca fascicularis; Male; Norepinephrine; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Receptors, Gastrointestinal Hormone; Receptors, Neurotransmitter; Receptors, Vasoactive Intestinal Peptide; Species Specificity; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) can be found at nerve endings in various tissues and has recently been shown to interact with human lymphocytes through an adenylate cyclase-linked receptor. Because various neuroendocrine factors are thought to influence immune responsiveness, we studied the effect of VIP on natural killer (NK) effector function. Human lymphocytes were incubated with 51Cr-labeled K562 target cells in a 4-hr cytotoxicity assay in the absence or presence of increasing concentrations of VIP. As expected from its activation of adenylate cyclase, VIP was inhibitory at 10(-6) to 10(-10) M. Interestingly, however, when lymphocytes were preincubated with VIP for 30 or 60 min, then washed and added to target cells, a significant augmentation of NK activity ensued. Binding studies revealed that preincubation with VIP resulted in increased numbers of effector-target conjugates, whereas cytotoxic activity in agarose was not affected at the single cell level. Studies with synthetic analogs of VIP revealed that the integrity of the 14-28 C-terminal amino acid sequence was essential for its activity in cytotoxicity. These data strongly suggest a functional role for VIP in modulating immune responses during neuroendocrine interactions with the immune system.

Topics: Cell Line; Cyclic AMP; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Humans; Immunosuppressive Agents; Killer Cells, Natural; Leukemia, Erythroblastic, Acute; Structure-Activity Relationship; Time Factors; Vasoactive Intestinal Peptide