EARLY BIOCHEMICAL EVENTS ASSOCIATED WITH LYMPHOCYTE-ACTIVATION IN AGING .1. EVIDENCE THAT CA-2+ DEPENDENT PROCESSES INDUCED BY PHA ARE IMPAIRED

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 42  (1) , 119-126
Abstract
The Ca2+ requirement, a divalent ion which plays a fundamental role in cell activation, was analyzed in cultures of PHA[phytohemagglutinin]-stimulated human peripheral blood lymphocytes (PHA-PBL) from adult (range: 20-35 yr) and old (over 70 yr) subjects. For this purpose, increasing concentrations of Ca2+ chelators (EGTA [ethyleneglycol-bis (.beta.-aminoethyl ether) N,N,N'',N''-tetraacetic acid] and EDTA) were added to cultures in order to compare the effect of progressive extracellular Ca2+ (Ca2+EC) [effective Ca2+ concentration] depletion of 3H-thymidine incorporation by PHA-PBL. Kinetic analysis showed that Ca2+EC requirement was restricted to the 1st 24 h after culture initiation. At optimal doses of PHA, the PHA-PBL from old subjects were more sensitive than those from adult subjects to increasing chelator concentrations. They also required larger Ca2+ supplement amounts to restore their normal response after total inhibition by EGTA. The PHA-PBL from the elderly were hypersensitive to verapamil (Isoptin), a drug which instigates a reversible inhibition of Ca2+-dependent processes associated with lymphocyte transformation, by a similar action to that induced by chelators. Evidently, the Ca2+-dependent processes in lymphocyte activation are impaired with aging. A deficiency of a late activation signal requiring cell-cell interactions in the elderly is possible.