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Published on: March 25, 2016
Effects of histamine on immunophenotype and notch signaling in human HL-60 leukemia cells
Li Mei Yu1, Dai Xiong Chen, Qi Xin Zhou
1The Key Laboratory of Cell Engineering in Guizhou Province, Affiliated Hospital of Zunyi Medical College, Zunyi Medical College, Zunyi, Guizhou Province, China. ylm6567@yahoo.com.cn
Insights
Histamine inhibits human leukemia cell growth and alters surface markers CD49d and CD31. These changes in immunophenotype occur independently of Notch signaling pathways.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Surface molecules are key biomarkers for cell proliferation, differentiation, and interaction.
- Notch signaling is crucial for developmental processes and cell-fate decisions.
- Histamine influences hematopoietic cell development and is used in leukemia immunotherapy.
Purpose of the Study:
- To investigate the effects of histamine on the immunophenotype and Notch signaling in human HL-60 leukemia cells.
- To determine if histamine's effects on leukemia cell growth and surface marker expression involve Notch signaling.
Main Methods:
- HL-60 leukemia cells were treated with varying concentrations of histamine.
- Cell proliferation was assessed using growth curves and colony-forming efficiency assays.
- Immunophenotypic changes were analyzed via flow cytometry, focusing on surface molecules like CD49d and CD31.
- Notch signaling pathway components (Notch1, Notch4, Jagged1, Delta4, HES1) were quantified using real-time RT-PCR.
Main Results:
- Histamine inhibited HL-60 cell growth in a dose-dependent manner.
- Histamine treatment significantly decreased CD49d expression by 74% and increased CD31 expression by 53%.
- Histamine did not significantly alter the expression of other tested surface molecules or key components of the Notch signaling pathway.
Conclusions:
- Histamine effectively inhibits HL-60 leukemia cell proliferation.
- Histamine modulates specific cell surface markers (CD49d and CD31), altering the immunophenotype.
- The observed immunophenotypic alterations induced by histamine in HL-60 cells are not mediated by the Notch signaling pathway.
Abstract:
Surface molecules are important biomarkers for cell proliferation and differentiation and play important roles in cell function and cell interaction. Notch is a transmembrane receptor that regulates developmental processes and cell-fate decision. Histamine is used as an adjunct to immunotherapy in myelogenous leukemia, and regulates hematopoietic cell development. Thus, we investigated the effects of histamine on immunophenotype and Notch signaling in human HL-60 leukemia cells. Histamine (0.1-10 microM) inhibited the colony-forming efficiency of HL-60 cells in a dose-dependent fashion and shifted the growth curve to the right. HL-60 cells were treated with histamine 0.1-1.0 microM for 6 days, and surface molecules were analyzed by flow cytometry. Histamine decreased CD49d positive cells by 74% while increasing CD31 positive cells by 53% as compared to controls. Histamine did not affect the expression of CD11b, CD14, CD34, CD44, CD54, CD49e, and CD62L. To examine Notch signaling in histamine-induced immunophenotype alterations in HL-60 cells, total RNA was isolated, purified, and subjected to real-time RT-PCR analysis. The expressions of Notch1, Notch4, the ligands Jagged1, Delta4, and the downstream hairy enhancer of split 1 gene (HES1) were not significantly altered by histamine. In summary, this study demonstrated that histamine inhibited HL-60 cell growth and regulated immunophenotypes of CD49d and CD31. These effects are not mediated through the Notch signaling.
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