Endogenous analgesia mediated by CD4+ T lymphocytes is dependent on enkephalins in mice

被引:43
作者
Basso, Lilian [1 ]
Boue, Jerome [1 ]
Mahiddine, Karim [2 ]
Blanpied, Catherine [1 ]
Robiou-du-Pont, Sebastien [1 ]
Vergnolle, Nathalie [1 ]
Deraison, Celine [1 ]
Dietrich, Gilles [1 ]
机构
[1] Univ Toulouse, UPS, ENVT, INRA,INSERM,IRSD, Toulouse, France
[2] Univ Toulouse, UPS, INSERM, CNRS,CPTP, Toulouse, France
关键词
T lymphocytes; Enkephalin; beta-endorphin; Inflammation; Pain; MU-OPIOID-RECEPTOR; PROOPIOMELANOCORTIN MESSENGER-RNA; BETA-ENDORPHIN; INFLAMMATORY PAIN; VISCERAL PAIN; CELL RESPONSE; LYMPH-NODES; RELEASE; EXPRESSION; INHIBITION;
D O I
10.1186/s12974-016-0591-x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: T cell-derived opioids play a key role in the control of inflammatory pain. However, the nature of opioids produced by T cells is still matter of debate in mice. Whereas beta-endorphin has been found in T lymphocytes by using antibody-based methods, messenger RNA (mRNA) quantification shows mainly mRNA encoding for enkephalins. The objective of the study is to elucidate the nature of T cell-derived opioids responsible for analgesia and clarify discrepancy of the results at the protein and genetic levels. Methods: CD4(+) T lymphocytes were isolated from wild-type and enkephalin-deficient mice. mRNA encoding for beta-endorphin and enkephalin was quantified by RT-qPCR. The binding of commercially available polyclonal anti-endorphin antibodies to lymphocytes from wild-type or enkephalin knockout mice was assessed by cytofluorometry. Opioid-mediated analgesic properties of T lymphocytes from wild-type and enkephalin-deficient mice were compared in a model of inflammation-induced somatic pain by measuring sensitivity to mechanical stimuli using calibrated von Frey filaments. Results: CD4(+) T lymphocytes expressed high level of mRNA encoding for enkephalins but not for beta-endorphin in mice. Anti-beta-endorphin polyclonal IgG antibodies are specific for beta-endorphin but cross-react with enkephalins. Anti-beta-endorphin polyclonal antibodies bound to wild-type but not enkephalin-deficient CD4(+) T lymphocytes. Endogenous regulation of inflammatory pain by wild-type T lymphocytes was completely abolished when T lymphocytes were deficient in enkephalins. Pain behavior of immune-deficient (i.e., without B and T lymphocytes) mice was superimposable to that of mice transferred with enkephalin-deficient lymphocytes. Conclusions: Rabbit polyclonal anti-beta-endorphin serum IgG bind to CD4(+) T lymphocytes because of their cross-reactivity towards enkephalins. Thus, staining of T lymphocytes by anti-beta-endorphin polyclonal IgG reported in most of studies in mice is because of their binding to enkephalins. In mice, CD4(+) T lymphocytes completely lose their analgesic opioid-mediated activity when lacking enkephalins.
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页数:10
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