Membrane-associated lymphotoxin-expressing lymphokine-activated killer cells up-regulate intercellular adhesion molecule-1 expression on target tumor cells in vitro.
Human lymphokine-activated killer (LAK) cells cultured with interleukin-2 express membrane-associated lymphotoxin (mLT) on the cell surface. mLT-lacking (mLT-) LAK cells, which are generated by culturing without IL-2 for 24 hr, fully retained natural killer (NK) and LAK activity. However, they partially lost their killing activity against various tumor cells when compared to mLT-expressing (mLT+) LAK cells. An anti-LT but not anti-tumor necrosis factor (TNF) antibody somewhat suppressed the killing activity of mLT+ LAK cells against these tumor cells. However, an anti-LT antibody did not alter NK or LAK activity of mLT+ LAK cells. Anti-CD18 (beta chain of LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies, by inhibiting LAK cell binding to targets, suppressed the killing activity of mLT+ LAK cells. During the process in the cytotoxic assay, mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target tumor cells, the effect of which was marginally inhibited by anti-TNF and anti-IFN-gamma but not by anti-LT antibodies. The up-regulation of ICAM-1 expression elicited by LAK cells on target tumor cells was not simply caused by diffused soluble factors but required membrane contact of LAK and target cells. Paraformaldehyde-fixed mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target cells. These findings indicate that mLT+ but not mLT- LAK cells up-regulate ICAM-1 expression on target tumor cells via undetermined membrane factor(s), and this effect appears to be at least partially responsible for the higher killing activity of mLT+ LAK cells than that of those lacking mLT in vitro.
Kimura
K
K
Second Department of Surgery, Ehime University School of Medicine, Japan.
Abe
Y
Y
Horiuchi
A
A
Miyake
M
M
Kimura
S
S
D000906:Antibodies / Q000494:pharmacology; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008233:Lymphotoxin-alpha / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology*
D000906:Antibodies; D016169:Lymphocyte Function-Associated Antigen-1; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1