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Published on: May 31, 2018
Functional expression of P2X family receptors in macrophages is affected by microenvironment in mouse T cell acute
Shayan Chen1, Wenli Feng1, Xiao Yang1
1State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Abstract:
Nucleotides are important players in intercellular signaling communication network. P2X family receptors (P2XRs) are ATP-gated plasma membrane ion channels with diverse biological functions. Macrophages are important components in the microenvironment of hematopoiesis participating in both physiological and pathological processes. However, the role of P2XRs in macrophages in leukemia has not been established. Here we investigated expression pattern and functions of P2XRs in macrophages from bone marrow (BM) and spleen of Notch1-induced T-ALL mice. Real-time PCR showed that P2XRs except P2X5R were expressed in BM and spleen macrophages. Furthermore, with the development of leukemia, the expression of P2X7R increased in both BM and spleen macrophages whereas expression of P2X1R increased in spleen macrophages. Live cell imaging recoding the Ca(2+) response demonstrated that P2X7R expressed in macrophages was functional. TUNEL and electron microscopy analysis found that apoptotic macrophages were frequently observed in BM and spleen at late stage of leukemia, which was partly contributed by the activation of overexpressed P2X7R. Our results suggested that the intercellular communication mediated by nucleotides might orchestrate in the pathological process of leukemia and could be a potential target for the treatment of leukemia.
Insights
Nucleotides and P2X receptors play roles in leukemia. Overexpressed P2X7 receptors on macrophages contribute to apoptosis in leukemia, suggesting a potential therapeutic target.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Nucleotides mediate intercellular communication via P2X receptors (P2XRs).
- Macrophages are crucial in hematopoiesis and disease, but their P2XR roles in leukemia are unknown.
- T-cell acute lymphoblastic leukemia (T-ALL) involves complex microenvironmental interactions.
Purpose of the Study:
- Investigate P2XRs in macrophages from leukemia-bearing mice.
- Determine P2XRs' function in macrophage apoptosis during leukemia progression.
- Assess P2XRs as potential therapeutic targets in leukemia.
Main Methods:
- Real-time PCR to analyze P2XR expression in bone marrow (BM) and spleen macrophages.
- Live cell imaging to assess calcium (Ca2+) responses mediated by P2XRs.
- TUNEL assay and electron microscopy to detect macrophage apoptosis.
Main Results:
- P2XRs (except P2X5R) are expressed in BM and spleen macrophages.
- Leukemia development increases P2X7R expression in macrophages and P2X1R in spleen macrophages.
- Activated P2X7R contributes to macrophage apoptosis in late-stage leukemia.
Conclusions:
- Nucleotide signaling via P2XRs influences leukemia pathology.
- Overexpressed P2X7R in macrophages promotes apoptosis, indicating a potential therapeutic target.
- Targeting nucleotide-mediated intercellular communication may offer new leukemia treatments.
