title: Phosphatidylserine receptor in chronic pancreatitis: evidence for a macrophage independent role.
abstract: OBJECTIVE
  This study analyzes the role of phosphatidylserine receptor (PSR) in chronic pancreatitis.
  
  
  BACKGROUND
  In chronic pancreatitis, destruction of parenchyma comes along with infiltration of lymphocytes and macrophages. The phosphatidylserine receptor is expressed on the surface of macrophages and is crucial for the recognition and engulfment of apoptotic cells. In the present study, we investigated the role of this receptor and its relation to apoptosis in chronic pancreatitis.
  
  
  METHODS
  The expression and localization of PSR were analyzed by Northern blot analysis, RT-PCR, Western blot analysis and immunohistochemistry. Apoptosis was detected by the TUNEL method, and the RNA protection assay (RPA) was used to compare activation of apoptosis with PSR mRNA expression levels. In addition, the molecular data were related to clinicopathological parameters.
  
  
  RESULTS
  PSR mRNA expression was low to absent in normal pancreatic tissue samples. In human chronic pancreatitis, increased expression of PSR mRNA was present in 12 of 29 samples (41%). Up-regulation of PSR could be confirmed by Western blot analysis. In chronic pancreatitis tissue, PSR immunoreactivity was present in all islets, in some ductal cells and in macrophages. The RNA protection assay revealed high mRNA levels of the antiapoptotic genes bcl-2 and bfl-1 (P < 0.05) in chronic pancreatitis tissues with high PSR mRNA expression. The TUNEL apoptosis in situ detection method showed positive signals in some redifferentiating acinar cells and focally in acinar cells adjacent to stromal fibroblasts in chronic pancreatitis tissue samples. The distribution pattern of PSR on pancreatic cells in chronic pancreatitis corresponded to a great extent with regions of high apoptotic activity.
  
  
  CONCLUSIONS
  We show for the first time the presence of PSR in chronic pancreatitis on pancreatic cells other than macrophages in regions with high apoptotic activity. The coexpression and colocalization of this gene with other apoptosis mediators suggest its involvement in apoptotic processes. However, in chronic pancreatitis PSR is not only involved in phagocytosis of apoptotic cells by macrophages.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Köninger
authors.forename: Peter
authors.initials: P
authors.lastname: Balaz
authors.forename: Markus
authors.initials: M
authors.lastname: Wagner
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.forename: Igor
authors.initials: I
authors.lastname: Cima
authors.forename: Arthur
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Pierluigi
authors.initials: P
authors.lastname: di Sebastiano
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D010195:Pancreatitis / Q000503:physiopathology*; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*
chemical_list: D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases