The amyloidogenic peptide human amylin augments the inflammatory activities of eosinophils.
The amyloidogenic peptides, amyloid-beta (A beta) and human amylin, are the major constituents of amyloid deposits found in patients with the chronic degenerative disorders Alzheimer's disease (AD) and type 2 diabetes, respectively. Recent studies have shown that a variety of inflammatory proteins such as cytokines are associated with the amyloid deposits of AD brain tissues. Therefore, in the present study, we sought to determine whether A beta and/or human amylin could modulate the various inflammatory activities of eosinophils. We observed that human amylin but not A beta peptides inhibited the in vitro interleukin-5 (IL-5)-mediated survival of cord blood-derived eosinophils (CBEs) in a concentration-dependent manner. By contrast, rat amylin, a nonamyloidogenic peptide that is highly homologous to human amylin, failed to affect the IL-5-mediated survival of CBEs. Similar inhibitory effects of human amylin were observed for peripheral blood eosinophils. Human amylin also enhanced the release of the cytokine granulocyte-macrophage colony-stimulating factor by CBEs that were stimulated with the calcium ionophore A23187 but was incapable of directly stimulating CBEs to release cytokines. In addition, the A23187-induced release of the inflammatory lipid mediator leukotriene C4 by CBEs was augmented by human amylin. These results suggest that the amyloidogenic peptide human amylin is capable of amplifying the various inflammatory activities of eosinophils.
Hom
J T
JT
Cardiovascular Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Estridge
T
T
Pechous
P
P
Hyslop
P A
PA
D000682:Amyloid / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004804:Eosinophils / Q000473:pathology*; D005312:Fetal Blood; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D017997:Leukotriene C4 / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D018836:Inflammation Mediators; D015848:Interleukin-5; D007476:Ionophores; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D017997:Leukotriene C4; D000001:Calcimycin