Expression of the adhesion molecules ICAM-1 and ICAM-2 on tumor cell lines does not correlate with their susceptibility to natural killer cell-mediated cytolysis: evidence for additional ligands for effector cell beta integrins.
The LFA-1 molecule (CD11a/CD18), a member of the leukocyte (beta 2) integrin subfamily of the integrin supergene family, has been shown to subserve important function(s) in natural killer (NK) and lymphokine-activated killer (LAK) effector cells based on monoclonal antibody inhibition and other studies. Presently, two cellular ligands for LFA-1 have been identified, termed ICAM-1 and ICAM-2. In this study, we have examined the role of target cell ICAM-1 (CD54) and ICAM-2 in NK-mediated target lysis. Using a panel of tumor target cell lines, ICAM-1 surface protein and transcript expression did not correlate with sensitivity to NK lysis. Compared to ICAM-1, ICAM-2 transcript expression was very low or undetectable in tumor cell targets, and also did not correlate with sensitivity to NK lysis. ICAM-1+ K562 cells and K562 cells which were rendered surface ICAM-1- with an antisense oligonucleotide were equally sensitive to NK lysis. Finally, human ICAM-1- P815 cells were stably transfected with the human ICAM-1 gene, and both ICAM-1- P815 (wild type) and ICAM-1+ stable transfectants were equally insensitive to NK lysis. These studies provide evidence that ICAM-1 and ICAM-2 are not important target cell ligands for NK effector cell LFA-1 and that other target cell ICAM may exist.
Akella
R
R
Guthrie Foundation for Medical Research, Guthrie Clinic/Medical Center, Sayre, PA 18840.
Hall
R E
RE
D000818:Animals; D015703:Antigens, CD; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology
D015703:Antigens, CD; D016375:Antisense Elements (Genetics); D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1