Blocking of human T lymphocyte activation by channel antagonists

Maria Rosa Bono, Valeska Simon, Mario S. Rosemblatt

Resultado de la investigación: Article

17 Citas (Scopus)

Resumen

It has been established that early events in lymphocyte activation involve a rise in intracellular Ca++ as well as changes in the flux of other ions. Although a Ca++ channel has been postulated to participate in the early Ca++ rise, its presence in lymphocytes remains controversial. Also although yet undetected, electrophysiological data suggest the presence of a Ca++ activated K+ channel on human peripheral blood lymphocytes (HPBL). Here we report on the effect of specific channel blockers as an approach to the identification of these channels on HPBL. At 40 nM nifedipine, an inhibitor of voltage‐gated Ca++ channels, fully inhibits the PHA‐promoted activation of HPBL. This effect is concentration dependant with a half maximum effect at approximately 10 nM and is demonstrable whether the drug is added at the same time as or up to 18 h after the addition of the mitogen. This inhibition of activation is not seen if the lymphocytes are activated using IL‐2 instead of PHA. Charybdotoxin a toxin which blocks a Ca++ activated K+ channel of muscle cells also blocks to almost 100 per cent the PHA‐induced activation of HPBL. This inhibition can be demonstrated regardless of whether the blocker is added together with or up to 4 h after PHA. As opposed to nifedipine charybdotoxin shows no effect if added 18 h after the initiation of the activation process. When nifedipine and charybdotoxin were tested on mice splenocytes we found that nifedipine fully inhibits the LPS‐promoted activation of these cells while charybdotoxin has no effect on their activation. Taken together these results strengthen the view regarding the participation of both a voltage‐gated Ca++ channel and a Ca++ activated K+ channel in human T lymphocyte activation.

Idioma originalEnglish
Páginas (desde-hasta)219-226
Número de páginas8
PublicaciónCell Biochemistry and Function
Volumen7
N.º3
DOI
EstadoPublished - 1 ene 1989

Huella dactilar

T-cells
Lymphocyte Activation
Lymphocytes
Charybdotoxin
Chemical activation
Nifedipine
T-Lymphocytes
Blood
Mitogens
Muscle Cells
Interleukin-2
Ions
Muscle
Cells
Fluxes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Bono, Maria Rosa ; Simon, Valeska ; Rosemblatt, Mario S. / Blocking of human T lymphocyte activation by channel antagonists. En: Cell Biochemistry and Function. 1989 ; Vol. 7, N.º 3. pp. 219-226.
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Blocking of human T lymphocyte activation by channel antagonists. / Bono, Maria Rosa; Simon, Valeska; Rosemblatt, Mario S.

En: Cell Biochemistry and Function, Vol. 7, N.º 3, 01.01.1989, p. 219-226.

Resultado de la investigación: Article

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AU - Simon, Valeska

AU - Rosemblatt, Mario S.

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N2 - It has been established that early events in lymphocyte activation involve a rise in intracellular Ca++ as well as changes in the flux of other ions. Although a Ca++ channel has been postulated to participate in the early Ca++ rise, its presence in lymphocytes remains controversial. Also although yet undetected, electrophysiological data suggest the presence of a Ca++ activated K+ channel on human peripheral blood lymphocytes (HPBL). Here we report on the effect of specific channel blockers as an approach to the identification of these channels on HPBL. At 40 nM nifedipine, an inhibitor of voltage‐gated Ca++ channels, fully inhibits the PHA‐promoted activation of HPBL. This effect is concentration dependant with a half maximum effect at approximately 10 nM and is demonstrable whether the drug is added at the same time as or up to 18 h after the addition of the mitogen. This inhibition of activation is not seen if the lymphocytes are activated using IL‐2 instead of PHA. Charybdotoxin a toxin which blocks a Ca++ activated K+ channel of muscle cells also blocks to almost 100 per cent the PHA‐induced activation of HPBL. This inhibition can be demonstrated regardless of whether the blocker is added together with or up to 4 h after PHA. As opposed to nifedipine charybdotoxin shows no effect if added 18 h after the initiation of the activation process. When nifedipine and charybdotoxin were tested on mice splenocytes we found that nifedipine fully inhibits the LPS‐promoted activation of these cells while charybdotoxin has no effect on their activation. Taken together these results strengthen the view regarding the participation of both a voltage‐gated Ca++ channel and a Ca++ activated K+ channel in human T lymphocyte activation.

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