Premium
Involvement of leukocyte (β2) integrins (CD18/CD11) in human monocyte tumoricidal activity
Author(s) -
Bernasconi Sergio,
Peri Giuseppe,
Sironi Marina,
Mantovani Alberto
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910490221
Subject(s) - cd18 , monocyte , cd11a , cytotoxicity , integrin alpha m , integrin , cell adhesion molecule , cd11c , monoclonal antibody , cytolysis , cytotoxic t cell , flow cytometry , tumor necrosis factor alpha , microbiology and biotechnology , lymphocyte function associated antigen 1 , biology , intercellular adhesion molecule 1 , chemistry , immunology , in vitro , receptor , antibody , biochemistry , phenotype , gene
Appropriately activated mononuclear phagocytes mediate contact‐dependent tumoricidal activity. Adhesion structures involved in contact‐dependent tumor cytotoxicity have not been defined. The present study was aimed at identifying the adhesion structures involved in the tumoricidal activity of activated (IFN‐γ + LPS) human monocytes. Tumor cells of different histological origin were used as targets in a 48‐hr cytolysis assay. Anti‐CD18 (integrin β2 chain) monoclonal antibodies (MAbs) substantially (50–40%) inhibited human monocyte cytotoxicity. When the role of different a‐chains was studied, anti‐αL (CD11a, LFA1), anti‐αM (CD11b, Mac‐1) and anti‐αX (CD11c, p150.95) caused marginal inhibition, but the effect of the 3 combined was comparable to that of anti‐CD18. Anti‐CD 18 MAb did not affect the release of various cytotoxic molecules (e.g. TNF) by activated human monocytes. Activated monocytes showed augmented binding to target cells and anti‐CD18 MAb inhibited the binding of resting and activated monocytes to tumor target cells. While IFN‐γ alone augmented expression of leukocyte integrins and LPS had no effect, the 2 activation signals, combined for optimal stimulation of tumoricidal activity, resulted in no appreciable increase in these leukocyte adhesion molecules, as assessed by flow cytometry. Our results suggest that the augmented CD 18‐dependent binding of activated monocytes on tumor cells depends mainly upon changes in the adhesive properties of these molecules rather than upon increased numbers on the cell surface. Anti‐1CAM‐1 MAb significantly reduced monocyte cytotoxicity on tumor cells, which is consistent with a role of the CD11/CD18 adhesion pathway. These results implicate “activated” leukocyte (β2) integrins (CD11 /CD18) as important adhesion molecules in the contact‐dependent tumoricidal activity of human monocytes.