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 (ie, attraction
and activation of these cells). To further evaluate this, we consecutively analyzed
the expression of 2 ligands of CCR5: RANTES and MIP-α. Methods. Pancreatic tissue samples of 22 patients with CP and of 7 healthy pancreas were evaluated.
CCR5, RANTES, and MIP-1α 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-1α 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-1α are concomitantly upregulated. (Surgery 2000;128:806-14.)
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References
- Course and outcome of chronic pancreatitis.Gastroenterology. 1984; 82: 820-828
- Chronic pancreatitis: clinical features and medical management.Am J Gastroenterol. 1986; 81: 153-167
- Pancreatic disease: a casualty of hepatic “detoxification”?.Lancet. 1983; 2: 1000-1003
- Pathogenesis and epidemiology of chronic pancreatitis.Annu Rev Med. 1989; 40: 453-468
- Pseudocysts in chronic pancreatitis: a morphological analysis of 57 resection specimens and 9 autopsy pancreata.Pancreas. 1991; 6: 266-274
- A short, eclectic history of exocrine pancreatic insufficiency and chronic pancreatitis.Gastroenterology. 1993; 104: 1255-1262
- Newer concept for the pathogenesis of chronic alcoholic pancreatitis.Am J Gastroenterol. 1977; 68: 278-285
- Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis.Gastroenterology. 1997; 112: 1656-1663
- Immunohistochemical characterization of pancreatic cellular infiltrate in normal pancreas, chronic pancreatitis and pancreatic carcinoma.Digestion. 1998; 59: 192-198
- Revised classification of pancreatitis: report of the Second International Symposium on the classification of pancreatitis in Marseille, France, March 28-30, 1984.Gastroenterology. 1985; 89: 683-685
- Classification of pancreatitis.Gut. 1984; 25: 756-759
- Lymphocyte subsets and HLA-DR expression in normal and chronic pancreatitis.Pancreas. 1990; 5: 415-420
- The molecular biology of leukocyte chemoattractant receptors.Annu Rev Immunol. 1994; 12: 593-633
- Identification of defensin-1, defensin-2 and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils.J Biol Chem. 1996; 271: 2935-2940
- Chemokines—chemotactic cytokines that mediate inflammation.N Engl J Med. 1998; 338: 436-445
- Chemokines and leukocyte traffic.Nature. 1998; 392: 565-568
- Cloning and characterization of a novel promiscuous human β-chemokine receptor D6.J Biol Chem. 1997; 272: 32078-32083
- Identification of single Cmotif-1/lymphotactin receptor XCR1.J Biol Chem. 1998; 273: 16551-16554
- High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome.Infect Immun. 1993; 61: 4553-4559
- Inflammatory cytokines in patients with persistence of the acute respiratory distress syndrome.Am J Respir Crit Care Med. 1996; 154: 602-611
- Cellular localization of the chemokine receptor CCR5.Am J Pathol. 1997; 151: 1341-1351
- Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque.Kidney Int. 1998; 54: 1945-1954
- Interferon-γ upregulates CCR5 expression in cord and adult blood mononuclear phagocytes.Blood. 1999; 93: 1137-1144
- CCR5 is characteristic of Th1 lymphocytes.Nature. 1998; 19: 568-574
- Enhanced expression of the type II transforming growth factor beta receptor in human pancreatic cancer cells without alteration of type III receptor expression.Cancer Res. 1993; 53: 2704-2707
- Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increase in levels of epidermal growth factor and transforming growth factor alpha.J Clin Invest. 1992; 90: 1353-1360
- Increased levels of phorbin, c-myc and ornithine decarboxylase RNAs in human colon cancer.Mol Carcinog. 1990; 3: 68-74
- Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization.Eur J Immunol. 1998; 28: 3696-3705
- A cDNA clone used to study mRNA inducible in human tonsillar lymphocytes by a tumor promoter.J Biochem. 1986; 99: 885-894
- A human Tcell-specific molecule is a member of a new gene family.J Immunol. 1988; 141: 1018-1025
- Suppression of endogenous avidinbinding activity in tissues and its relevance to biotinavidin detection systems.J Histochem Cytochem. 1981; 29: 1196-1204
- Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding.J Exp Med. 1997; 186: 1373-1381
- Expression of the C-C chemokine receptor 5 in human kidney diseases.Kidney Int. 1999; 56: 52-64
- Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-α, MIP-β, and RANTES.J Leukocyte Biol. 1996; 60: 147-152
- Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine receptors.J Exp Med. 1996; 184: 2433-2438
- Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes.J Exp Med. 1997; 185: 969-974
- Selective inhibition of expression of the chemokine receptor CCR2 in human monocytes by IFN-γ.J Immunol. 1998; 160: 3869-3873
- Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation.Eur J Immunol. 1998; 28: 2760-2769
- Multistep navigation and the combinatorial control of leukocyte chemotaxis.J Cell Biol. 1997; 139: 1349-1360
- Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease.J Leukocyte Biol. 1997; 62: 604-611
- Differential expression of chemokines in normal pancreas and in chronic pancreatitis.Gastroenterology. 2000; 118: 356-367
- A molecular switch of chemokine receptor selectivity. Chemical modification of the inter leukin-8 Leu2→Cys mutant.J Biol Chem. 1996; 271: 3148-3153
- Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes.J Exp Med. 1996; 184: 569-577
- CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis.Am J Gastroenterol. 1998; 93: 2141-2147
Article info
Publication history
Accepted:
May 7,
2000
Footnotes
*Supported by Swiss National Foundation grant 32-049494.
***The first 2 authors have equally contributed to this work.
★Reprint requests: Helmut Friess, MD, Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, CH-3010 Bern, Switzerland.
★★Surgery 2000;128:806-14.
Identification
Copyright
© 2000 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
