title: Macrophages infiltrating the tissue in chronic pancreatitis express the chemokine receptor CCR5.
abstract: BACKGROUND
  The immunologic mechanisms involved in the development of chronic pancreatitis (CP) are poorly understood. Chronically inflamed tissues contain increased numbers of mononuclear cells expressing the CC chemokine receptor 5 (CCR5), which is also a coreceptor for HIV entry of macrophagetropic strains. However, whether this receptor is involved in the inflammatory process in CP is not known. In the current study, we analyzed the expression of CCR5 in CP. The detection of chemokine receptors on inflammatory cells would strongly suggest their involvement in the pathogenesis of CP (i.e., attraction and activation of these cells). To further evaluate this, we consecutively analyzed the expression of 2 ligands of CCR5: RANTES and MIP-alpha.
  
  
  METHODS
  Pancreatic tissue samples of 22 patients with CP and of 7 healthy pancreas were evaluated. CCR5, RANTES, and MIP-1alpha were analyzed by Northern blot analysis. Consecutive tissue sections were stained for CCR5, CD3, and CD68 to define the leukocyte subtype expressing CCR5 in CP.
  
  
  RESULTS
  By Northern blot analysis, CCR5, RANTES, and MIP-1alpha messenger RNA (mRNA) levels were 12.9-fold, 13.3-fold and 9.2-fold higher in CP specimens compared with healthy controls, respectively (P<.01). Immunostaining for CCR5 revealed a 30-fold increase of CCR5-positive cells in CP tissue compared with the healthy pancreas. Staining of consecutive tissue sections revealed that the majority of CCR5-positive cells were also CD68-positive (macrophages).
  
  
  CONCLUSIONS
  Our data indicate that a remarkable portion of CCR5-positive cells in CP are macrophages. CCR5 is most likely involved in the attraction and activation of these macrophages, since the CCR5 ligands RANTES and MIP-1alpha are concomitantly upregulated.
authors.affiliation: Department of Visceral and Transplantation Surgery, the Theodor-Kocher Institute, and the Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Goecke
authors.forename: U
authors.initials: U
authors.lastname: Forssmann
authors.forename: M
authors.initials: M
authors.lastname: Uguccioni
authors.forename: H
authors.initials: H
authors.lastname: Friess
authors.forename: J R
authors.initials: JR
authors.lastname: Conejo-Garcia
authors.forename: A
authors.initials: A
authors.lastname: Zimmermann
authors.forename: M
authors.initials: M
authors.lastname: Baggiolini
authors.forename: M W
authors.initials: MW
authors.lastname: Büchler
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015152:Blotting, Northern; D017252:CD3 Complex / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism* / Q000473:pathology*; D019713:Receptors, CCR5 / Q000378:metabolism*; D012016:Reference Values; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; C067980:CD68 antigen, human; D000097382:CD68 Molecule