International Immunology, Vol 10, 981-989, Copyright © 1998 by Oxford University Press
E Mariani, AR Mariani, A Meneghetti, A Tarozzi, L Cocco and A Facchini
The progressive increase in the number of peripheral NK cells found in the
elderly does not correlate with a corresponding increase in lytic activity.
On the contrary, a decreased function of circulating NK cells purified from
old subjects was observed on a per cell basis. Most of the studies on NK
cells have focused on late events such as lytic activity. In view of this,
little is currently known about the modification of the early signalling
pathways of NK cells in elderly people. This study investigated whether the
modification of NK lytic activity could be related to differences in the
metabolic pattern of activation of these cells in the elderly. NK cells
were negatively purified by immunomagnetic depletion from the peripheral
blood of selected old and young healthy subjects. Hydrolysis of inositol
phospholipids was measured following incubation with K562 target cells
and/or CD16 mAb for different times. Our data show that there is a
pronounced age-related decrease in the ability to generate total inositol
monophosphates and, particularly, inositol trisphosphates by NK cells
following K562 stimulation (spontaneous cytolytic activity) together with
an attenuated and delayed hydrolysis of phosphatidylinositol bisphosphate,
while phosphoinositide turnover is preserved following Fc triggering
(antibody-dependent cell-mediated cytotoxicity). These results confirm
that, also in old subjects, different biochemical pathways of activation
are involved in NK cells when target or antibody-mediated triggering occurs
and may aid the development of experimental and therapeutic strategies to
counteract declines in cell mediated immune functions associated to
advancing age.
ARTICLES
Age-dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc-mediated cytolytic activity
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla- Putti, IOR, Bologna, Italy.
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