Abstract
The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation.
| Original language | English |
|---|---|
| Journal | BBA General Subjects |
| Volume | 972 |
| Issue number | 3 |
| Pages (from-to) | 257-64 |
| Number of pages | 8 |
| ISSN | 0304-4165 |
| Publication status | Published - 1988 |
Keywords
- Acquired Immunodeficiency Syndrome
- Benzofurans
- Calcimycin
- Calcium
- Cell Division
- Cytoplasm
- Drug Interactions
- Fluorescent Dyes
- Fura-2
- Humans
- Interleukin-2
- Lymphocytes
- Phytohemagglutinins
- Plant Extracts
- Receptors, Interleukin-2
- Spectrometry, Fluorescence
- Tetradecanoylphorbol Acetate
- Thapsigargin
