title: CD14+ monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2 diabetes.
abstract: 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 assessed how immune-mediating peripheral blood mononuclear cells (PBMCs) are affected in diabetes.
  
  
  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.
authors: Disease Control and Homeostasis, Kanazawa University, Graduate School of Medical Science, Kanazawa, Japan.
authors: Takuya
authors: T
authors: Komura
authors: Yoshio
authors: Y
authors: Sakai
authors: Masao
authors: M
authors: Honda
authors: Toshinari
authors: T
authors: Takamura
authors: Kouji
authors: K
authors: Matsushima
authors: Shuichi
authors: S
authors: Kaneko
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000473:pathology*; D004198:Disease Susceptibility / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors