Inhibition of the lytic activity of perforin by lipoproteins.
Cytoplasmic granules isolated from cytolytic T lymphocytes (CTL) lyse red blood cells or tumor cell lines in a nonspecific manner. The activity of highly purified granules was inhibited by human or rabbit serum at dilutions as high as 1/10,000. The main inhibitory activity of human serum was isolated by chromatography and was determined to be high density lipoprotein (HDL). HDL not only inhibited at a concentration of 70 ng/ml the lytic activity of isolated granules, but also of the purified, pore-forming protein perforin present in the granules. Purified low density lipoprotein was equally active. Because the CTL granule activity was inhibited by pure egg lecithin vesicles at a concentration equivalent to the phospholipid content of lipoproteins, the lipid portion of lipoproteins is the likely candidate for granule inactivation. Lipoproteins also decreased in a dose-dependent manner the cytotoxic activity of intact cytolytic T cells. However, cytotoxicity was not completely suppressed, and only in the case of CTL exhibiting low efficiency in killing their targets. It is proposed that lipoproteins inactivate perforin and may thereby inhibit a possible lysis of innocent bystander cells.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007473:Ion Channels; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin