Transmembrane signaling changes with aging.

Altered immune response and transmembrane signaling with aging has previously been demonstrated. The aim of the present study was to characterize PMNLs and lymphocyte G proteins and to determine whether their relative amounts are altered with aging. First we studied the effects of FMLP on PMNLs IP3 formation. It was found that in any group of elderly the PMNLs IP3 formation was significantly decreased compared to that of young subjects. In FMLP receptor binding affinity no measurable difference exists in either low- or high-affinity FMLP receptors. The autoradiogram of 32P-ADP-ribosylated proteins by CT in lymphocytes of young individuals showed a major polypeptide of 40 kDa, and two much less prevalent components of 52 and 45 kDa. In contrast, in lymphocytes of elderly subjects the major polypeptide was 45 kDa, and the two others were very weakly labeled. In PMNLs, CT labeled the 45-kDa band quite strongly, mainly in the elderly, and the 52- and 40-kDa bands were very weakly labeled, mainly in young subjects. When PT was used, no age-related pattern changes could be demonstrated, while differences could be observed between the two types of cells.

Altered post-receptorial signal transduction mechanism under various stimulation in polymorphonuclear granulocytes of Alzheimer's disease.

The cyclic nucleotide changes were studied under 10(-6) M isoproterenol (IP), 10(-6) M carbachol and 10(-8) M Met-enkephalin (Met-enk) stimulations in polymorphonuclear granulocytes (PMNLs) of middle-aged (aged 35-52 years) and elderly (aged 61-97 years) healthy subjects, as well as of patients with Alzheimer's disease (AD) (aged 58-65 years). From our results we can conclude that in the case of middle-aged healthy subjects only the IP caused a marked cAMP elevation while in elderly and AD all the applied substances stimulated the cAMP at different degrees. Concerning the cGMP levels in PMNLs, we observed a marked increase under carbachol and Met-enk stimulation, in middle-aged subjects, while in the elderly a weak change was obtained by carbachol. In AD practically no change of cGMP levels could be obtained. Thus, the main features of AD are a cAarP response to Met-enk and an abolition of a GarP response to carbachol. We can conclude that in PMNLs of elderly and patients with AD we assist to an altered post-receptorial signal transduction mechanism, which seems to be even more marked in the case of AD comparing to normal aging.

Impaired coupling of naloxone sensitive opiate receptors to adenylate cyclase in PMNLs of aged male subjects.

Met-enkephalin (Met-enk) in 10(-9)-10(-7) M concentrations enhanced the extracellular cytotoxicity of polymorphonuclear leukocytes (PMNL) of young adult humans partly by stimulation of the "respiratory burst" in these cells. Meanwhile adenylate cyclase was inhibited and guanylate cyclase was stimulated. All the observed effects were abolished by 10(-5) M naloxone. On the other hand, a positive receptor coupling to adenylate cyclase was found when Met-enk was added in higher (10(-6)-10(-5) M) concentrations to PMNLs. The elevated cAMP level resulted in decreased extracellular cytotoxicity of PMNLs by a naloxone insensitive way. In PMNLs obtained from healthy aged male subjects, Met-enk induced in all of the applied concentrations an increased cAMP level and no change in cGMP level, with subsequent decrease of cytotoxicity, i.e. an impaired negative coupling of naloxone sensitive opiate receptors was detected with aging.

New method for detecting bacteriocin production.

Bacteriocin production can be easily detected by using both sides of the agar contained in a standard petri dish.