Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the potential effects of technical pentachlorophenol (PCP-T, contaminated with polychlorinated dioxins and furans) and of analytical grade pentachlorophenol (PCP-A) on the human immune system, in vitro assays with freshly prepared human peripheral blood lymphocytes were used as an alternative to experimental animals. Both cell-mediated and humoral immune functions were examined after direct lymphocyte exposure to PCP-T or PCP-A at concentrations ranging from 0-200 microM. In each case the viability of the treated cells remained within the control value range. T lymphocyte blastogenesis after 3 days incubation with PCP was measured using both optimal and suboptimal mitogen (PHA) concentration. Interleukin-2 activity of 24.5-h supernatants of lymphocytes in response to PHA, pretreated with PCP for 20-24 h, was examined in a bioassay using the mouse IL-2-dependent CTLL-6 cell line. The synthesis of immunoglobulins was determined after stimulation with T-dependent (PWM) and T-independent (KlebsM) polyclonal B cell activators. In the proliferation assay the effects of PCP-T became more evident after suboptimal mitogen stimulation. Whereas after optimal mitogen stimulation blastogenesis was affected only at the highest concentration of 200 microM PCP-T, cell reactivity after suboptimal PHA stimulation was altered by all PCP-T doses. In the lower concentration range PCP-T caused enhanced proliferative responses, but at the two highest PCP-T concentrations cell reactivity was significantly suppressed as compared to the medium controls. Significant differences between the effects of PCP-T and PCP-A could be demonstrated only after optimal mitogen stimulation at the highest PCP concentration (200 microM). In contrast, lymphokine production as well as Ig secretion showed severe dose-dependent suppression after exposure to both PCP-T and PCP-A. The humoral immune response appeared to be more suppressed when cultures were stimulated with T-dependent rather than T-independent mitogens. The two different PCP preparations caused immunosuppression of both lymphocyte functions to the same extent. To summarize, the results of our studies indicate that PCP itself is directly immunotoxic to human immunocompetent cells and the T helper cell subset appears to be especially sensitive to PCP exposure. Furthermore, the observation of a direct effect on humoral immunity is similar to previous results showing considerable alterations of antigen specific antibody production in experimental animals after in vivo exposure.
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PMID:Human lymphocyte reactivity after in vitro exposure to technical and analytical grade pentachlorophenol. 177 35

The psychotomimetic drug PCP displays a vast array of known pharmacological effects, among them its capacity to affect cation transport in nervous and myocardiac tissues. Since increased movements of cations are essential for the immune responses, it has been mentioned that PCP could also depress immune functions by this mechanism. In order to check this hypothesis, we have investigated the effects of PCP and of many other structural derivatives on the blastogenic response of murine or human T lymphocytes. We find that all the drugs block an early event of T lymphocyte activation and prevent their further proliferation; conversely they do not affect primed lymphocytes. The compounds, which do not inhibit interleukin-1 (IL-1) production in stimulated macrophages, lower interleukin-2 (IL-2) synthesis in activated T helper cells. This negative action appears to be related to the inhibition of the rise of free cytosolic calcium concentration [Ca2+]i observed soon after the T receptor triggering and which is an essential message for IL-2 production. The lymphocyte membrane depolarization induced by the drugs could explain the blockade of the lectin-induced [Ca2+]i changes. The study of the structure-activity relationship shows that the PCP analogs which possess a quasi-rigid conformational structure express an inhibitory capacity of T lymphocyte proliferation higher than that of PCP (200 times for some products). Since these compounds interact poorly with the CNS tissues and have few behavioral effects, we suggest that PCP exerts its negative action on lymphocytes on cell components different from its receptor(s) in the CNS.
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PMID:PCP and analogs prevent the proliferative response of T lymphocytes by lowering IL2 production. An effect related to the blockade of mitogen-triggered enhancement of free cytosolic calcium concentration. 296 41

Pneumonia due to Pneumocystis carinii (PCP) is regularly encountered in organ allograft recipients who are immunosuppressed to prevent rejection. Recipients of lung/heart allografts may be particularly prone to pulmonary infection due to systemic immunosuppression and the fact that defense mechanisms in the transplanted lung may be further impaired through tissue incompatibility and the effects of surgery. In this study, we monitored 16 lung transplant recipients for infection with Pneumocystis carinii using serial bronchoalveolar lavage (BAL) and found the prevalence of Pneumocystis infection of the lung to be 88%. Six episodes were associated with the usual symptoms of pneumonia, whereas 10 episodes were associated with minimal or no symptoms. In 3 of the 6 symptomatic episodes, a concurrent bacterial infection was also found. The total number of cells recovered from the lung by BAL, the proportion of T-lymphocytes, and the number of cytotoxic/suppressor and helper/inducer cells were elevated during infection with Pneumocystis compared to before and after. Spontaneous and interleukin-2-induced proliferation of BAL cells in vitro was also higher during infection, suggesting that there was an increased number of activated T-lymphocytes in the airspaces of the infected allograft. BAL cells cultured with irradiated spleen cells from the donor proliferated at higher levels when obtained after Pneumocystis infection than when obtained before or during infection even for subclinical infections. These results indicate that in the absence of prophylaxis, the prevalence of Pneumocystis infestation is very high after lung/heart transplantation. Impaired defense of the transplanted lung does not seem to stem from the inability of activated T-lymphocytes to accumulate in the allograft.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unexpectedly high incidence of Pneumocystis carinii infection after lung-heart transplantation. Implications for lung defense and allograft survival. 314 96