Endogenous analgesia mediated by CD4(+) T lymphocytes is dependent on enkephalins in mice.
J Neuroinflammation
; 13(1): 132, 2016 06 01.
Article
em En
| MEDLINE
| ID: mdl-27245576
ABSTRACT
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 ß-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 ß-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 ß-endorphin in mice. Anti-ß-endorphin polyclonal IgG antibodies are specific for ß-endorphin but cross-react with enkephalins. Anti-ß-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-ß-endorphin serum IgG bind to CD4(+) T lymphocytes because of their cross-reactivity towards enkephalins. Thus, staining of T lymphocytes by anti-ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Medição da Dor
/
Encefalinas
/
Linfócitos T CD4-Positivos
/
Analgesia
Limite:
Animals
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França