CD14＋monocytes are vulnerable and functionally impaired under ER stress in patients with type 2 diabetes

フォーマット:

論文

責任表示:

Komura, Takuya ; Sakai, Yoshio ; Honda, Masao ; Takamura, Toshinari ; Matsushima, Kouji ; Kaneko, Shuichi

言語:

英語

出版情報:

American Diabetes Association, 2010-03-01

著者名:

Komura, Takuya

Sakai, Yoshio

Honda, Masao

Takamura, Toshinari

Matsushima, Kouji

Kaneko, Shuichi

続きを見る

掲載情報:

Diabetes

ISSN:

0012-1797      

巻:

59

通号:

3

開始ページ:

634

終了ページ:

643

バージョン:

author

概要:

金沢大学医薬保健研究域医学系<br />OBJECTIVE - Although patients with diabetes suffer from increased infections and a higher incidence of cancer due to impaired immune function, details on diabetes-induced decrease in immunity are lacking. We assess … ed how immune-mediating peripheral blood mononuclear cells (PBMCs) are affected in diabetes. RESEARCH DESIGN AND METHODS - From 33 patients with type 2 diabetes and 28 healthy volunteers, we obtained PBMCs and investigated their susceptibility to apoptosis and functional alteration. RESULTS - In a subpopulation of PBMCs, monocytes derived from patients with diabetes were more susceptible to apoptosis than monocytes from healthy volunteers. Monocytes from patients with diabetes had decreased phagocytotic activity and were less responsive to Toll-like receptor (TLR) ligands, although the expression of TLRs did not differ significantly between the two groups. Furthermore, monocytes from patients with diabetes had a distinctly different gene expression profile compared with monocytes from normal volunteers as assessed with DNA microarray analysis. Specifically, quantitative real-time detection PCR measurements showed an elevated expression of the markers of endoplasmic reticulum (ER) stress in diabetic monocytes, and electron microscopic examination of monocytes revealed morphologic alterations in the ER of cells derived from patients with diabetes. Consistently, the ER stress inducer tunicamycin increased apoptosis of otherwise healthy monocytes and attenuated the proinflammatory responses to TLR ligands. CONCLUSIONS - These data suggest that monocytes comprise a substantially impaired subpopulation of PBMCs in patients with diabetes and that ER stress is involved in these pathologic changes mechanistically. This implies that the affected monocytes should be investigated further to better understand diabetic immunity. © 2010 by the American Diabetes Association. 続きを見る

URL:

http://hdl.handle.net/2297/23966