THE AMYLOIDOGENIC PEPTIDE HUMAN AMYLIN AUGMENTS THE INFLAMMATORY ACTIVITIES OF EOSINOPHILS

The amyloidogenic peptides, amyloid-beta (A beta) and human amylin, ar e the major constituents of amyloid deposits found in patients with th e chronic degenerative disorders Alzheimer's disease (AD) and type 2 d iabetes, respectively. Recent studies have shown that a variety of inf lammatory proteins such as cytokines are associated with the amyloid d eposits of AD brain tissues. Therefore, in the present study, we sough t to determine whether A beta and/or human amylin could modulate the v arious inflammatory activities of eosinophils, We observed that human amylin but not A beta peptides inhibited the in vitro interleukin-5 (I L-5)-mediated survival of cord blood-derived eosinophils,(CBEs) in a c oncentration-dependent manner. By contrast, rat amylin, a nonamyloidog enic peptide that is highly homologous to human amylin, failed to affe ct the IL-5-mediated survival of CBEs, Similar inhibitory effects of h uman amylin were observed for peripheral blood eosinophils. Human amyl in also enhanced the release of the cytokine granuloeyte-macrophage co lony-stimulating factor by CBEs that were stimulated with the calcium ionophore A23187 but was incapable of directly stimulating CBEs to rel ease cytokines, In addition, the A23181-induced release of the inflamm atory lipid mediator leukotriene C-4 by CBEs was augmented by human am ylin, These results suggest that the amyloidogenic peptide human amyli n is capable of amplifying the various inflammatory activities of eosi nophils.