The role of LFA-1 in the lysis of bladder cancer cells by bacillus Calmette-Guérin and interleukin 2-activated killer cells.
Activated cytotoxic effector cells such as bacillus Calmette-Guérin (BCG)-activated killer (BAK) and lymphokine-activated killer (LAK) cells are thought to mediate the antitumor effects in the immunotherapy of superficial bladder cancer with BCG. We investigated the role of the leukocyte-function-antigen-1 and its two subunits CD11a and CD18 in the lysis of bladder tumor cells by both effector cell populations. We used flow cytometry to measure CD11a and CD18 expression on BAK and LAK cells. The involvement of both surface molecules in the lysis of bladder tumor cells was determined by phase contrast microscopy and a set of radioactive-release assays using specific inhibitory antibodies. BAK and LAK cells expressed more CD11a and CD18 on their surfaces than unstimulated peripheral blood mononuclear cells. Effector-target cell adhesion was a prerequisite for the cell-mediated cytotoxicity of BAK and LAK cells against bladder tumor targets. Cytotoxicity of both BAK and LAK cells was inhibited by a combination of anti-CD11a and -CD18 monoclonal antibodies. Our study gives further insight into the complex interactions of the adhesion molecules of activated immune cells and their respective tumor targets and might help to increase our knowledge of the molecular mechanisms of BCG-immunotherapy.
Department of Urology, Medical University of Lübeck, Germany.
Henrik
H
Suttmann
Dieter
D
Jocham
Andreas
A
Böhle
Sven
S
Brandau
D040881:CD11a Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D009163:Mycobacterium bovis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000503:physiopathology*
D040881:CD11a Antigen; D018821:CD18 Antigens; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1