Hemopexins suppress phorbol ester-induced necrosis of polymorphonuclear leucocytes.
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.
Suzuki
K
K
Department of Biology, School of Education, Waseda University, Tokyo, Japan. kingo@mn.waseda.ac.jp
Kato
H
H
Sakuma
Y
Y
Namiki
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006466:Hemopexin / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009336:Necrosis; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D012709:Serum Albumin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014462:Ultrafiltration
D000970:Antineoplastic Agents; D012709:Serum Albumin; D013481:Superoxides; D006466:Hemopexin; D013755:Tetradecanoylphorbol Acetate