Hemopexins suppress phorbol ester-induced necrosis of polymorphonuclear leucocytes

Cell Struct Funct. 2001 Aug;26(4):235-41. doi: 10.1247/csf.26.235.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / antagonists & inhibitors*
  • Cattle
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Hemopexin / isolation & purification
  • Hemopexin / metabolism
  • Hemopexin / pharmacology*
  • Humans
  • Necrosis
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Serum Albumin / pharmacology
  • Superoxides / metabolism
  • Swine
  • Tetradecanoylphorbol Acetate / antagonists & inhibitors*
  • Ultrafiltration

Substances

  • Antineoplastic Agents
  • Serum Albumin
  • Superoxides
  • Hemopexin
  • Tetradecanoylphorbol Acetate