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)

T lymphocytes are potentially of importance in determining the inflammatory response in the airways after allergen challenge. We hypothesized that the proliferative response of lymphocytes on exposure to allergen in vitro would be associated with the magnitude of the airway response in vivo after inhalational challenge. We studied Brown Norway rats that were actively sensitized with ovalbumin (OA) in aluminum hydroxide gel using Bordetella pertussis as an adjuvant. Two weeks later, blood mononuclear cells were isolated, and their proliferative response to culture with OA was measured with 3H-thymidine incorporation. Subsequently, the animals were anesthetized and challenged with aerosolized OA. Early allergic response (ER) and late (LR) allergic response were determined from the changes in pulmonary resistance (RL). Both significant ER and LR were observed in sensitized and challenged animals. The LR (measured as the area under the curve of RL against time) had a median value of 15.2 and ranged from 0.1 to 81.1 units. Lymphocyte proliferation occurred on exposure to OA (34,336 +/- 7,447 cpm) but less than after the mitogen Concanavalin A (250,685 +/- 76,676 cpm). The stimulation index (OA-stimulated 3H-thymidine incorporation standardized for baseline incorporation) was positively correlated with the magnitude of the late response. Interleukin-2 was significantly increased in the supernatant of cultured mononuclear cells exposed to OA, confirming T-cell activation. We conclude that the capacity of sensitized peripheral blood lymphocytes to respond to allergens may determine the magnitude of late airway responses.
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PMID:Association between late allergic bronchoconstriction in the rat and allergen-stimulated lymphocyte proliferation in vitro. 784 8

Interleukin-2 (IL-2) plays a vital role in the generation and regulation of the immune response, including important aspects of T cell survival. IL-2-mediated survival of T cells appears to be dependent on the activation of a pool of membrane-associated protein kinase C (PKC) that occurs in the absence of detectable translocation of the enzyme from the cytosol to membranes. In this report we investigate the mechanism(s) responsible for this PKC activation after IL-2 stimulation in the cytotoxic T cell line, CTLL-2. Tyrosine kinase activity, activated after IL-2 stimulation, was found not to be linked to the activation of PKC by the cytokine. On the other hand, a pertussis toxin (PTX)-sensitive G protein did appear coupled to PKC activation since PTX effectively blocked IL-2 stimulated PKC activity. Diacylglycerols (DAG), but not inositol 1,3,5-triphosphate (IP3) and intracellular Ca2+, increased after IL-2 stimulation suggesting that DAGs were generated via the phosphatidylcholine-phospholipase C (PC-PLC) or phosphatidylcholine-phospholipase D (PC-PLD) pathways. The increase in DAG by IL-2 was probably necessary for activation of membrane-resident PKC since exogenously applied DAG stimulated this PKC pool in both intact cells and in isolated membranes. IL-2 also increased arachidonic acid (AA) production in CTLL-2 cells, probably via phospholipase A2 (PLA2) since the PLA2 inhibitors oleoyloxyethyl phosphocholine and AACOCF3 (AACF) effectively blocked IL-2 stimulated PKC activation. Exogenous AA also increased PKC activity in intact cells and isolated membranes, suggesting that AA produced by IL-2 receptor stimulation was probably linked to PKC activation. These results suggest that the activation of membrane-resident PKC by IL-2 involves multiple second messengers, including G proteins, DAG and AA.
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PMID:Signalling events mediating the activation of protein kinase C by interleukin-2 in cytotoxic T cells. 1037 5

Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis has previously shown that the P2Y(14) receptor is expressed in peripheral immune cells including lymphocytes. Although in transfected cells the P2Y(14) receptor couples to pertussis toxin-sensitive G(i/o) protein, the functional coupling of endogenously expressed P2Y(14) receptors to the inhibition of adenylyl cyclase activity has not been reported. Therefore, the primary aim of this study was to determine whether the P2Y(14) receptor is functionally expressed in murine spleen-derived T- and B-lymphocyte-enriched populations. RT-PCR analysis detected the expression of P2Y(14) receptor mRNA in whole spleen and isolated T- and B-lymphocytes. In T cells, UDP-glucose (EC(50) = 335 nM) induced a small but significant inhibition (circa 20%) of forskolin-stimulated cAMP accumulation, suggesting functional coupling of endogenously expressed P2Y(14) receptors to the inhibition of adenylyl cyclase activity. In contrast, the other putative P2Y(14) receptor agonists UDP-galactose, UDP-glucuronic acid and UDP-N-acetylglucosamine had no significant effect alone but behaved as partial agonists by blocking UDP-glucose responses. In B cells, UDP-glucose (100 microM) had no significant effect on forskolin-stimulated cAMP accumulation. Treatment of T cells with pertussis toxin (G(i/o) blocker) abolished the inhibitory effects of UDP-glucose on forskolin-stimulated cAMP accumulation. T-cell proliferation in response to anti-CD3 monoclonal antibody (1 microg ml(-1)) was significantly inhibited by UDP-glucose (59% inhibition; p[IC(50)] = 5.9 +/- 0.3), UDP-N-acetylglucosamine (37%; 6.1 +/- 0.3), UDP-galactose (56%; 8.2 +/- 0.2) and UDP-glucuronic acid (49%; 6.3 +/- 0.2). Interleukin-2- (5 ng ml(-1)) induced T-cell proliferation was also significantly inhibited by all four agonists. In summary, we have shown that the P2Y(14) receptor appears to be functionally expressed in murine spleen-derived T-lymphocytes. These observations suggest that UDP-glucose and related sugar nucleotides presumably via the P2Y(14) receptor may play an important role in modulating immune function.
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PMID:Functional expression of the P2Y14 receptor in murine T-lymphocytes. 1599 28