Cytotoxic liposomes: membrane interleukin 1 presented in multilamellar vesicles.
Paraformaldehyde-fixed lipopolysaccharide (LPS)-activated human monocytes produced significant lysis of the human melanoma cell line A375. The cytotoxic activity was retained following treatment of the fixed monocytes with anti-tumor necrosis factor (anti-TNF) antibodies but was specifically inhibited by a mixture of anti-TNF and anti-interleukin 1 (anti-IL 1) antibodies. A375 cells were also killed by plasma membranes purified from LPS-activated human blood monocytes. This activity was specifically inhibited by anti-IL 1 alpha antibodies, but only partially inhibited by anti-IL 1 beta antibodies. CHAPS detergent-extracted plasma-membrane IL 1 in its soluble form or associated with lyophilized liposomes was also able to kill A375 cells, and this antitumor activity was inhibited by anti-IL 1 antibodies. These results suggest that membrane IL 1, primarily IL 1 alpha, was cytotoxic for the A375 cells. CKS-17, a peptide synthesized with homology to a highly conserved region of the immunosuppressive retroviral envelope protein P15E, when covalently bound to BSA partially inhibited the IL 1 activities of tumor cell cytotoxicity and T-cell clone proliferation, displayed by purified plasma membranes, detergent-extracted membrane IL 1, or membrane IL 1 associated with liposomes. These findings indicate that cytotoxic membrane IL 1 can be solubilized by detergent, bound to the surface of liposomes, and specifically inhibited by anti-IL 1 antibodies or the immunosuppressive peptide CKS-17.
Bakouche
O
O
Department of Cell Biology, M.D. Anderson Hospital, Houston, TX 77030.
Lachman
L B
LB
Knowles
R D
RD
Kleinerman
E S
ES
D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000096:biosynthesis / Q000302:isolation & purification; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes; D008545:Melanoma / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000276:immunology
D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008081:Liposomes; D010455:Peptides; C053692:CKS 17