PLUG AND SEAL - PREVENTION OF HYPOXIC CARDIOCYTE DEATH BY SEALING MEMBRANE LESIONS WITH ANTIMYOSIN-LIPOSOMES


KHAW B., TORCHILIN V., VURAL İ. , NARULA J.

NATURE MEDICINE, cilt.1, sa.11, ss.1195-1198, 1995 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 1 Konu: 11
  • Basım Tarihi: 1995
  • Doi Numarası: 10.1038/nm1195-1195
  • Dergi Adı: NATURE MEDICINE
  • Sayfa Sayıları: ss.1195-1198

Özet

The hallmark of cell death is the development of cell membrane lesions. Such lesions in the myocardium are usually associated with acute myocardial infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy constitutes the only major treatment to date. We envisioned a method to seal these membrane lesions using immunoliposomes as a novel adjunctive approach. An antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is used as an anchoring site, and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are cardiocytes and are propagated in tissue culture and their viability may be assessed by various methods. Viability assessed by [H-3]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue exclusion and by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by targeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological systems.