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(Journal of Leukocyte Biology. 2000;68:873-880.)
© 2000 by Society for Leukocyte Biology

Spontaneous apoptosis in neutrophils is associated with downregulation of HLA Class I and is prevented by ligation of Class I

Guido Frumento, Luciano Ottonello^*, Maria Bertolotto^*, Silvia Franchello, Giovanni Melioli and Franco Dallegri^*

Immunogenetics Laboratory and
Flow Cytometry Unit, National Institute for Cancer Research, Genoa, Italy; and
^* Department of Internal Medicine, University of Genoa, Genoa, Italy

Correspondence: Guido Frumento, M.D., Immunogenetics Laboratory, National Cancer Institute c/o Advanced Biotechnology Center A2, Largo Rosanna Benzi 10, 16132 Genova, Italy. E-mail: frumento{at}ermes.cba.unige.it

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.

Key Words: human • neutrophils • age-related • apoptosis

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