Immunocytes and activated stellate cells in pancreatic fibrogenesis

Pancreas. 2003 Apr;26(3):239-42. doi: 10.1097/00006676-200304000-00006.


Introduction and aims: Chronic pancreatitis is a progressive chronic inflammatory disease characterized by irreversible destruction of exocrine pancreatic tissue and extensive fibrosis. Excessive alcohol consumption has been identified as the main etiologic factor of this disease in the Western world. Idiopathic pancreatitis accounts for approximately 30% of cases. An autoimmune mechanism may be involved in some patients, but this concept has not been generally accepted as a new clinical entity. The purpose of this work was to investigate the pathogenesis of pancreatic fibrosis and to establish the role of immunocytes and activated stellate cells in chronic pancreatitis, which was categorized into three groups: chronic alcoholic pancreatitis (AP), chronic idiopathic pancreatitis (IP), and chronic pancreatitis in the presence of pancreatic cancer (CA).

Methodology: Fifty-one pancreatic tissue samples were studied histopathologically and immunohistochemically (AP, 16 samples; IP, 12; CA, 12; and samples of tissue with apparently normal pancreatic histology, 11). The following immunohistochemical stains were used: alpha-smooth muscle antibody, desmin, and synaptophysin, as markers of activated stellate cells; and laminin, fibronectin, and collagen IV, as markers of extracellular matrix (ECM) proteins. Immunocytes were stained with antibody to LCA, CD68 antibody (macrophages), and CD8 antibody (natural killer T cell subset), and mast cells were examined using the Giemsa method. Positively stained macrophages, lymphocytes, and mast cells were counted in three high-power fields of a light microscope. The immunoreactivity of activated stellate cells and ECM proteins was assessed by a semiquantitative method (0, lack of positive staining; 5, numerous cells with strong positive immunostaining). Results were assessed statistically.

Results: We found no statistical differences between cases of AP, IP, and CA in terms of total lymphocyte count (mean numbers: 416, 418, and 407 per three high-power fields, respectively). The percentage of CD8+ T cells in IP was statistically higher than that in AP. The macrophage count was significantly higher in the IP group than in the AP and CA groups. The mast cell count was markedly higher in the IP group than in the other groups. The stellate cell markers alpha-smooth muscle antibody and desmin showed slightly higher immunoreactivity in IP. The immunopositivity for synaptophysin was also higher in the IP group. There was a positive correlation between alpha-smooth muscle antibody, desmin, and synaptophysin expression and the degree of fibrosis. ECM protein markers showed no statistically significant differences between the three groups.

Conclusion: Results of this work show that a significant number of IP cases might have an autoimmune etiology. There was a positive correlation between activated stellate cell marker expression and the degree of fibrosis.

MeSH terms

  • Cell Count
  • Chronic Disease
  • Extracellular Matrix Proteins / analysis
  • Fibrosis
  • Humans
  • Lymphocytes / cytology
  • Macrophages / cytology
  • Mast Cells / cytology
  • Monocytes / cytology
  • Pancreas / cytology
  • Pancreas / immunology
  • Pancreas / pathology*
  • Pancreatic Neoplasms / complications
  • Pancreatitis / complications
  • Pancreatitis / immunology*
  • Pancreatitis / pathology*


  • Extracellular Matrix Proteins