Apparent membrane pore-formation by Portuguese Man-of-war (Physalia physalis) venom in intact cultured cells.
Intracellular, ratiometric microfluorimetry with fura-2 reveals that low doses of Portuguese Man-of-war (Physalia physalis) venom cause a linear increase in intracellular calcium accumulation by cultured L-929 cells. The influx of calcium is preceded by a lag period that is relatively independent of venom concentration, except at very low concentrations. Electron micrographs of negatively stained preparations of membranes from venom-treated L-929 and GH(4)C(1) cells exhibit 10-80 nm diameter lesions. The number and diameter of these lesions correlate with venom concentration. The venom forms lesions in GH(4)C(1) cells at much lower concentrations than in L-929 cells. Osmotic protectants such as sucrose and polyethylene glycol (PEG), reduce the extent of lactate dehydrogenase (LDH) release from venom-treated cells with the higher molecular weight PEG causing a greater inhibition of LDH release than sucrose. These results imply that Man-of-war venom produces pore-like structures in the membranes of target cells, which leads to colloid osmotic swelling with subsequent release of intracellular proteins and cell lysis.
Edwards
Lincoln P
LP
Department of Physiology and Pharmacology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Whitter
Ernest
E
Hessinger
David A
DA
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D003064:Cnidarian Venoms / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D037402:Hydrozoa; D007473:Ion Channels / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009995:Osmosis; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D013395:Sucrose / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003064:Cnidarian Venoms; D004338:Drug Combinations; D007473:Ion Channels; D011092:Polyethylene Glycols; D013395:Sucrose; D007770:L-Lactate Dehydrogenase