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Published on: July 28, 2016
Hemopexins suppress phorbol ester-induced necrosis of polymorphonuclear leucocytes
1Department of Biology, School of Education, Waseda University, Tokyo, Japan. kingo@mn.waseda.ac.jp
Abstract:
It was recently reported that intravenous administration of phorbol 12-myristate 13-acetate (PMA) showed a therapeutic effect in myelocytic leukemia patients. However, we previously observed that, in serum-free conditions, polymorphonuclear leucocytes (PMNs) were killed rapidly by exposure to PMA, suggesting the possibility of serious side effects. In this study, we found that PMA-induced necrosis of PMNs was prevented by serum, suggesting the existence of a "necrosis-suppressing factor". Next we tried to identify the serum factor. The hemopexins we purified were found to suppress necrosis of PMNs in a dose-dependent fashion. Hemopexins alone could not suppress necrosis, however, as it required the coexistence of another macromolecule such as albumin. Albumin promoted the suppressive activity of hemopexins in a dose-dependent fashion. These results strongly suggest that serum hemopexins may rescue mature PMNs from necrosis in the PMA-administered leukemia patient as previously reported, resulting in avoidance of serious side effects.
Insights
Serum hemopexins, with albumin, prevent phorbol 12-myristate 13-acetate (PMA) from causing polymorphonuclear leucocyte (PMN) necrosis. This finding suggests a way to avoid serious side effects in leukemia patients treated with PMA.
Area of Science:
- Biochemistry
- Hematology
- Cell Biology
Background:
- Phorbol 12-myristate 13-acetate (PMA) shows therapeutic potential for myelocytic leukemia.
- PMA can cause rapid polymorphonuclear leucocyte (PMN) death in serum-free conditions, indicating potential side effects.
Purpose of the Study:
- To identify the serum factor responsible for preventing PMA-induced PMN necrosis.
- To investigate the protective role of serum components against PMA toxicity in PMNs.
Main Methods:
- Investigated the effect of serum on PMA-induced PMN necrosis.
- Purified serum hemopexins and assessed their ability to suppress PMN necrosis.
- Examined the role of albumin in conjunction with hemopexins.
Main Results:
- Serum prevented PMA-induced necrosis of PMNs, indicating a protective factor.
- Purified hemopexins suppressed PMN necrosis in a dose-dependent manner.
- Hemopexin's protective effect required the presence of albumin, which enhanced the suppression.
Conclusions:
- Serum hemopexins, in conjunction with albumin, protect mature PMNs from PMA-induced necrosis.
- This mechanism may prevent serious side effects in leukemia patients undergoing PMA treatment.
- Identified a potential therapeutic strategy to mitigate PMA toxicity in cancer therapy.
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