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      Both Substance P and Its Receptor Are Expressed in Mouse Intestinal T Lymphocytes

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          Substance P (SP), one of the most prevalent neuropeptides in gut, has been reported to have potent immune modulatory effects as a proinflammatory agent. The synthesis of SP and SP receptor expression in intraepithelial and lamina propria T lymphocytes of mouse intestine was investigated. Using RT-PCR analysis, it was demonstrated that SP receptor mRNA was exclusively expressed in intraepithelial and lamina propria T lymphocytes as well as their purified CD4+, CD8+ and CD4–CD8–CD3+ subsets. Messenger RNAs (mRNAs) for the two precursors of SP, β and γ-preprotachykinin-A, were also detected. These results were consistent in lymphocytes from both epithelium and lamina propria of small and large intestines, although the frequencies and/or intensities of mRNA expression varied. However, none of the findings could be repeated in splenic T lymphocytes. Activation of splenocytes with anti-CD3Ε-chain mAb and PMA did not induce expression of SP or its receptor mRNAs. Furthermore, both cytoplasmic and surface-bound SP was demonstrated in intestinal T lymphocytes using dual color immunocytochemistry and immunoflow cytometry. In vitro treatment with SP did not significantly change the size of the SP-immunoreactive T cell population, indicating the presence of SP receptor on intestinal T lymphocytes as well as in vivo binding of endogenously released SP. Our data suggest that SP production and SP receptor expression are distinctive for mouse intestinal mucosal immunity and that SP may act as a modulator of an ongoing controlled inflammation in normal gut, by acting through its specific receptor on T lymphocytes in an autocrine and/or paracrine pattern.

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          Contrasting levels of variability between cytoplasmic genomes and incompatibility types in the mosquito Culex pipiens.

          Reproductive incompatibilities called cytoplasmic incompatibilities are known to affect a large number of arthropod species and are mediated by Wolbachia, a maternally transmitted microorganism. The crossing relationships between strains of potential hosts define their incompatibility types and it is generally assumed that differences between strains of Wolbachia induce different crossing types. Among all the described host species, the mosquito, Culex pipiens, displays the greatest variability of cytoplasmic incompatibility crossing types. We analysed mitochondrial and bacterial DNA variability in Culex pipiens in order to investigate some possible causes of incompatibility crossing type variability. We sequenced fragments of the ftsZ gene, and the A + T-rich control region of the mtDNA. We also sequenced the second subunit of the mitochondrial cytochrome oxidase (COII) gene, in Culex pipiens and a closely related species, C. torrentium, in order to verify the usefulness of the A + T-rich region for the present purposes. No variability was found in the Wolbachia ftsZ gene fragment, and very limited variation of the mitochondrial marker whatever the compatibility type or the origin of the host. A low variability was found in the A + T-rich region and comparison of divergence of the A + T-rich region and COII gene between C. pipiens and C. torrentium did not reveal any special constraints affecting this region. In contrast to observations in other host species, variability of incompatibility crossing types is not due to multiple infections by distantly related Wolbachia strains.
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            Tachykinins in the gut. Part II. Roles in neural excitation, secretion and inflammation.

            The preprotachykinin-A gene-derived peptides substance (substance P; SP) and neurokinin (NK) A are expressed in intrinsic enteric neurons, which supply all layers of the gut, and extrinsic primary afferent nerve fibers, which innervate primarily the arterial vascular system. The actions of tachykinins on the digestive effector systems are mediated by three different types of tachykinin receptor, termed NK1, NK2 and NK3 receptors. Within the enteric nervous system, SP and NKA are likely to mediate, or comediate, slow synaptic transmission and to modulate neuronal excitability via stimulation of NK3 and NK1 receptors. In the intestinal mucosa, tachykinins cause net secretion of fluid and electrolytes, and it appears as if SP and NKA play a messenger role in intramural secretory reflex pathways. Secretory processes in the salivary glands and pancreas are likewise influenced by tachykinins. The gastrointestinal arterial system may be dilated or constricted by tachykinins, whereas constriction and an increase in the vascular permeability are the only effects seen in the venous system. Various gastrointestinal disorders are associated with distinct changes in the tachykinin system, and there is increasing evidence that tachykinins participate in the hypersecretory, vascular and immunological disturbances associated with infection and inflammatory bowel disease. In a therapeutic perspective, it would seem conceivable that tachykinin antagonists could be exploited as antidiarrheal, antiinflammatory and antinociceptive drugs.
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              Eosinophils within the healthy or inflamed human intestine produce substance P and vasoactive intestinal peptide.

              The purpose of this study was to show if inflammatory cells within healthy or diseased human intestinal mucosa produce some regulatory neuropeptides. First, inflammatory cells were isolated from the intestinal lamina propria of 11 patients with ulcerative colitis or Crohn's disease. Also collected were cells from anatomically normal intestine derived from five patients requiring bowel resection for diseases not related to inflammatory bowel disease. Extracts of these isolated cells contained authentic substance P (SP) and vasoactive intestinal peptide (VIP) as shown by RIA and their elution profiles on HPLC. Immunostaining of cells from nine of 13 additional patients localized immunoreactive SP and VIP to secretory granules within most mucosal eosinophils. No other cell types stained positive. Messenger RNA encoding SP and VIP was localized to lamina propria eosinophils by in situ hybridization. Mucosa inflammatory cells, from eight of nine more patients, cultured in vitro, released detectable amounts of VIP, but not SP. It is concluded that intestinal eosinophils produce SP and VIP. Since the eosinophils store and release more VIP than SP, it is possible that VIP is the preferred secretory product.

                Author and article information

                S. Karger AG
                May 2001
                31 May 2001
                : 73
                : 5
                : 358-368
                Departments of aMedicine and bImmunology, Umeå University, Umeå, Sweden
                54653 Neuroendocrinology 2001;73:358–368
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 6, Tables: 2, References: 47, Pages: 11
                Peripheral Neuroendocrinology


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