Abstract
Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA, induced significant cytolysis of B lymphoma cells compared with Lym-1 and PMA alone. The effect of PMA was independent of the ability of the compound to stimulate neutrophil-respiratory burst. In fact, first, neutrophils from a patient with chronic granulomatous disease were cytolytically effective in spite of their inability to produce oxidants. Second, various kinase inhibitors exerted different effects on the PMA-stimulated cytolytic system and neutrophil-oxidative burst. Previous studies have shown the involvement of the FcgammaRII, CD11b-CD18 integrins, and CD66b glycoproteins in the Lym-1 mAb-dependent cytolysis by GM-CSF-stimulated neutrophils. The present PMA-stimulated system was inhibited by the anti-FcgammaRII mAb IV.3, the anti-CD18 mAb MEM 48, and the anti-CD11b mAb 2LPM19c but not by the anti-CD66b mAb 80H3 and N-acetyl-D-glucosamine. Furthermore, the PMA- and GM-CSF-stimulated cytolysis was insensitive and sensitive to inhibition by pertussis toxin, respectively. Thus, the use of PMA and GMCSF as neutrophil stimulants uncovers the existence of distinct mechanisms of Lym-1 mAb-mediated cytolysis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adjuvants, Immunologic / pharmacology
-
Antibodies, Monoclonal / immunology*
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Monoclonal, Murine-Derived
-
Antibody-Dependent Cell Cytotoxicity / drug effects
-
Antibody-Dependent Cell Cytotoxicity / immunology*
-
Antigens, CD
-
Antigens, Neoplasm*
-
B-Lymphocytes / cytology
-
B-Lymphocytes / immunology*
-
Burkitt Lymphoma / immunology*
-
Burkitt Lymphoma / pathology
-
CD18 Antigens / immunology
-
Cell Adhesion Molecules*
-
GPI-Linked Proteins
-
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
-
Humans
-
Macrophage-1 Antigen / immunology
-
Membrane Glycoproteins / immunology
-
Neutrophil Activation / drug effects
-
Neutrophil Activation / immunology
-
Neutrophils / drug effects
-
Neutrophils / immunology*
-
Pertussis Toxin
-
Receptors, IgG / immunology*
-
Signal Transduction / drug effects
-
Signal Transduction / immunology
-
Tetradecanoylphorbol Acetate / pharmacology
-
Virulence Factors, Bordetella / pharmacology
Substances
-
Adjuvants, Immunologic
-
Antibodies, Monoclonal
-
Antibodies, Monoclonal, Murine-Derived
-
Antigens, CD
-
Antigens, Neoplasm
-
CD18 Antigens
-
CEACAM8 protein, human
-
Cell Adhesion Molecules
-
GPI-Linked Proteins
-
Lym-1 monoclonal antibody
-
Macrophage-1 Antigen
-
Membrane Glycoproteins
-
Receptors, IgG
-
Virulence Factors, Bordetella
-
Granulocyte-Macrophage Colony-Stimulating Factor
-
Pertussis Toxin
-
Tetradecanoylphorbol Acetate