Spontaneous apoptosis in neutrophils is associated with downregulation of HLA Class I and is prevented by ligation of Class I.
In many types of cells, ligation of human leukocyte antigens (HLA) Class I molecules with specific mAbs results in the transduction of signals that trigger different cell functions. We have investigated the effects of Class I ligation in human neutrophils. After several hours in culture, neutrophils split spontaneously into two subpopulations, one with normal and the other with reduced levels of Class I. The latter subpopulation displayed high binding capacity for Annexin V, showed a hypodiploid peak, electrophoretic DNA fragmentation, and morphological features of apoptotic cells. The addition of drugs known to delay apoptosis (GM-CSF or cAMP) resulted in a reduction of Class I modulation. Furthermore, ligation of surface Class I with F(ab')2 fragments of the anti-Class I mAb W6/32 resulted in a delay in the progression of apoptosis. These data indicate that this surface Class I molecule is a marker of age-related apoptosis, and the ligation of these molecules results in the transduction of a signal that inhibits apoptosis. Thus, the downregulation of HLA Class I molecules in aging neutrophils prevents their halting the apoptotic process.
Frumento
G
G
Immunogenetics Laboratory, National Institute for Cancer Research, Genoa, Italy. frumento@ermes.cba.unige.it
Ottonello
L
L
Bertolotto
M
M
Franchello
S
S
Melioli
G
G
Dallegri
F
F
D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016922:Cellular Senescence; D000242:Cyclic AMP / Q000494:pharmacology; D053938:DNA Fragmentation; D015536:Down-Regulation; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D016256:Lewis X Antigen / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D017452:Receptors, IgG / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017304:Annexin A5; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007140:Immunoglobulin Fab Fragments; D016256:Lewis X Antigen; D017452:Receptors, IgG; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate