| Autor: |
Stenke, Leif, Mansour, Mahmoud, Reizenstein, Peter, Lindgren, Jan Ake |
| Zdroj: |
Blood; January 1993, Vol. 81 Issue: 2 p352-356, 5p |
| Abstrakt: |
The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4or LTB4to the cultures dose-dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10−8mol/L, at which LTC4induced a 91 % ± 23% (mean ± SEM; P= .004) and LTB4a 73% ± 22% (P= .008) increase in colony formation. In contrast, addition of the LTB4isomer 5(S), 12(S)-diHETEdid not affect the growth. LTD4exerted a weak potentiating effect on progenitor proliferation (17% ±7% growth stimulation at 10−10mol/L; P= .034), whereas LTE4was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4or LTC4. The results suggest that both LTB4and LTC4possess strong and specific synergistic stimulatory effects on GM-CSF–induced human myeloid progenitor cell growth. |
| Databáze: |
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