Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphoid cells of the mammalian immune system exhibit special migratory properties within their in vivo environment. This fundamental characteristic is important to the protection of the organism from infection and neoplastic transformation by a process termed immunologic surveillance. The importance of lymphocyte recirculation was addressed by investigating the role of site-selective homing of lymphocytes during the efferent phase of an in vivo adoptively transferred immune response. We approached this problem by using pertussis toxin (PT), a known inhibitor of lymphoid cell migration in vivo. PT is a protein secreted by the bacterium Bordetella pertussis, which induces a selective and long-lasting inhibition of the emigration of lymphocytes from the bloodstream into solid tissue. In this study, we demonstrate that the blockade of lymphocyte extravasation potential mediates inhibition of certain cell-mediated immune responses in vivo. We investigated the effect of PT on the extravasation of antigen-primed lymphocytes into solid tissue. The results show that the loss of lymphocyte homing potential after in vitro treatment of the primed cells with PT is accompanied by an inhibition of antigen-specific contact hypersensitivity after adoptive transfer. This result suggests that the process of lymphocyte extravasation into nonlymphoid tissue sites such as the skin shares fundamental similarities to the selective localization of circulating lymphocytes to lymph nodes. Furthermore, the inhibition of contact hypersensitivity observed after the i.v. adoptive transfer of PT-treated antigen-primed cells could be circumvented by transferring the PT-treated cells directly into a tissue site with the relevant antigen. In contrast, no inhibition in the number of antibody-forming cells present within the spleen was observed after an adoptive transfer of PT-treated sheep red blood cell-primed lymphocytes, a result that is in agreement with radiotracer data. Thus, the inhibitory effect of PT on the adoptive transfer of contact hypersensitivity was established to be a direct result of the PT-mediated alteration of cellular migration, because PT inhibits the entrance of lymphocytes into specific tissue sites without inhibiting other cellular functions. This conclusion is additionally supported by experiments that showed that lymphocytes that have been pretreated with PT exhibit normal in vitro responses, as assayed by mitogenesis in response to concanavalin A and by the differentiation and function of alloantigen stimulated or hapten-specific cytotoxic T lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Site-selective homing of antigen-primed lymphocyte populations can play a crucial role in the efferent limb of cell-mediated immune responses in vivo. 403 88

Exocytosis in neuroendocrine cells, such as chromaffin cells, is under the regulatory control of heterotrimeric G proteins. LDCV from bovine adrenal medulla contains alpha o-, beta-, and gamma-subunits of G-protein heterotrimers. Probably G proteins associated with the secretory vesicles control the final steps of secretion. G(o), associated with LDCV, could be the pertussis toxin-sensitive G protein that either inhibits exocytosis in PC12 cells or activates it in chromaffin cells. So far, it is unclear whether the other effects of GTP analogues are mediated by heterotrimeric G proteins or by small GTP-binding proteins. The other type of secretory vesicle, SSV from rat brain, also possesses functional sets of G-protein heterotrimers, each consisting of an alpha-, a beta- and a gamma-subunit. In addition to alpha o-subunits, however, alpha i-subunits were found on SSV. Their functional role remains to be determined. Thus, two types of secretory vesicles of the regulated pathway possess functional sets of G-protein heterotrimers. Besides exocytosis, heterotrimeric G proteins on secretory vesicles may control their maturation, transmitter storage, and endocytotic retrieval. So far, it is unclear whether the pattern of G proteins on LDCV and SSV analogues differs within various types of neuroendocrine cells and whether it will change after neoplastic transformation. An altered G-protein setup, not only at the plasma membrane but also on secretory vesicles, may play a role in pathophysiological processes occurring in neuroendocrine cells and tumors derived from them. Such changes might explain the altered secretion observed in neuroendocrine tumor diseases.
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PMID:Requirements for exocytosis in permeabilized neuroendocrine cells. Possible involvement of heterotrimeric G proteins associated with secretory vesicles. 797 79