Expression of S100A12 (EN-RAGE) in cystic fibrosis.
PDF (226K)
+3 authors
Journal: 2003/August - Thorax
ISSN: 0040-6376
PUBMED: 12832680
Abstract:
BACKGROUND
Chronic airway inflammation and recurrent infections are a core phenomenon in cystic fibrosis (CF). Diagnosing acute infectious exacerbations is difficult in the presence of chronic inflammatory processes. S100A12 exhibits proinflammatory functions via interaction with the multiligand receptor for advanced glycation end products. Blocking this interaction inhibits inflammatory processes in mice.
METHODS
The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured.
RESULTS
Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml).
CONCLUSIONS
S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(27)
References
(34)
Diseases
(3)
Chemicals
(3)
Organisms
(1)
Anatomy
(1)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
Thorax 58(7): 613-617
PMID: 12832680

Expression of S100A12 (EN-RAGE) in cystic fibrosis

Abstract

Methods: The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured.

Results: Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml).

Conclusions: S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.

Full Text

The Full Text of this article is available as a PDF (226K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075–1082. [PubMed] [Google Scholar]
  • Accurso FJ. Early pulmonary disease in cystic fibrosis. Curr Opin Pulm Med. 1997 Nov;3(6):400–403. [PubMed] [Google Scholar]
  • Dakin C, Henry RL, Field P, Morton J. Defining an exacerbation of pulmonary disease in cystic fibrosis. Pediatr Pulmonol. 2001 Jun;31(6):436–442. [PubMed] [Google Scholar]
  • Smith AL, Redding G, Doershuk C, Goldmann D, Gore E, Hilman B, Marks M, Moss R, Ramsey B, Rubio T, et al. Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis. J Pediatr. 1988 Apr;112(4):547–554. [PubMed] [Google Scholar]
  • Ilg EC, Troxler H, Bürgisser DM, Kuster T, Markert M, Guignard F, Hunziker P, Birchler N, Heizmann CW. Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry. Biochem Biophys Res Commun. 1996 Aug 5;225(1):146–150. [PubMed] [Google Scholar]
  • Vogl T, Pröpper C, Hartmann M, Strey A, Strupat K, van den Bos C, Sorg C, Roth J. S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J Biol Chem. 1999 Sep 3;274(36):25291–25296. [PubMed] [Google Scholar]
  • Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999 Jun 25;97(7):889–901. [PubMed] [Google Scholar]
  • Yang Z, Tao T, Raftery MJ, Youssef P, Di Girolamo N, Geczy CL. Proinflammatory properties of the human S100 protein S100A12. J Leukoc Biol. 2001 Jun;69(6):986–994. [PubMed] [Google Scholar]
  • Robinson MJ, Hogg N. A comparison of human S100A12 with MRP-14 (S100A9). Biochem Biophys Res Commun. 2000 Sep 7;275(3):865–870. [PubMed] [Google Scholar]
  • Yeh CH, Sturgis L, Haidacher J, Zhang XN, Sherwood SJ, Bjercke RJ, Juhasz O, Crow MT, Tilton RG, Denner L. Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diabetes. 2001 Jun;50(6):1495–1504. [PubMed] [Google Scholar]
  • Lander HM, Tauras JM, Ogiste JS, Hori O, Moss RA, Schmidt AM. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J Biol Chem. 1997 Jul 11;272(28):17810–17814. [PubMed] [Google Scholar]
  • Frosch M, Strey A, Vogl T, Wulffraat NM, Kuis W, Sunderkötter C, Harms E, Sorg C, Roth J. Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum. 2000 Mar;43(3):628–637. [PubMed] [Google Scholar]
  • van den Bos C, Rammes A, Vogl T, Boynton R, Zaia J, Sorg C, Roth J. Copurification of P6, MRP8, and MRP14 from human granulocytes and separation of individual proteins. Protein Expr Purif. 1998 Aug;13(3):313–318. [PubMed] [Google Scholar]
  • Watkin SL, Elborn JS, Cordon SM, Hiller EJ, Shale DJ. C-reactive protein is not a useful indicator of intermittent bacterial colonization in early lung disease of patients with cystic fibrosis. Pediatr Pulmonol. 1994 Jan;17(1):6–10. [PubMed] [Google Scholar]
  • Wolter JM, Rodwell RL, Bowler SD, McCormack JG. Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis. Clin Diagn Lab Immunol. 1999 Mar;6(2):260–265.[PMC free article] [PubMed] [Google Scholar]
  • Koller DY, Götz M, Wojnarowski C, Eichler I. Relationship between disease severity and inflammatory markers in cystic fibrosis. Arch Dis Child. 1996 Dec;75(6):498–501.[PMC free article] [PubMed] [Google Scholar]
  • Valletta EA, Rigo A, Bonazzi L, Zanolla L, Mastella G. Modification of some markers of inflammation during treatment for acute respiratory exacerbation in cystic fibrosis. Acta Paediatr. 1992 Mar;81(3):227–230. [PubMed] [Google Scholar]
  • Nixon LS, Yung B, Bell SC, Elborn JS, Shale DJ. Circulating immunoreactive interleukin-6 in cystic fibrosis. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1764–1769. [PubMed] [Google Scholar]
  • De Rose V, Oliva A, Messore B, Grosso B, Mollar C, Pozzi E. Circulating adhesion molecules in cystic fibrosis. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1234–1239. [PubMed] [Google Scholar]
  • Kähler CM, Prior C, Gunsilius E. Serum vascular endothelial growth factor is elevated in cystic fibrosis and decreases with treatment of acute pulmonary exacerbation. Am J Respir Crit Care Med. 2001 Mar;163(4):1030–1031. [PubMed] [Google Scholar]
  • Eichler I, Nilsson M, Rath R, Enander I, Venge P, Koller DY. Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis. Eur Respir J. 1999 Nov;14(5):1145–1149. [PubMed] [Google Scholar]
  • Karpati F, Hjelte FL, Wretlind B. TNF-alpha and IL-8 in consecutive sputum samples from cystic fibrosis patients during antibiotic treatment. Scand J Infect Dis. 2000;32(1):75–79. [PubMed] [Google Scholar]
  • Francoeur C, Denis M. Nitric oxide and interleukin-8 as inflammatory components of cystic fibrosis. Inflammation. 1995 Oct;19(5):587–598. [PubMed] [Google Scholar]
  • Grasemann H, Ioannidis I, Tomkiewicz RP, de Groot H, Rubin BK, Ratjen F. Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child. 1998 Jan;78(1):49–53.[PMC free article] [PubMed] [Google Scholar]
  • Boussac M, Garin J. Calcium-dependent secretion in human neutrophils: a proteomic approach. Electrophoresis. 2000 Feb;21(3):665–672. [PubMed] [Google Scholar]
  • Clohessy PA, Golden BE. Elevated plasma levels of L1L and L1H in CF patients. Biochem Soc Trans. 1996 May;24(2):310S–310S. [PubMed] [Google Scholar]
  • Golden BE, Clohessy PA, Russell G, Fagerhol MK. Calprotectin as a marker of inflammation in cystic fibrosis. Arch Dis Child. 1996 Feb;74(2):136–139.[PMC free article] [PubMed] [Google Scholar]
  • Roth J, Goebeler M, Sorg C. S100A8 and S100A9 in inflammatory diseases. Lancet. 2001 Mar 31;357(9261):1041–1041. [PubMed] [Google Scholar]
  • Lügering N, Stoll R, Schmid KW, Kucharzik T, Stein H, Burmeister G, Sorg C, Domschke W. The myeloic related protein MRP8/14 (27E10 antigen)--usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function. Eur J Clin Invest. 1995 Sep;25(9):659–664. [PubMed] [Google Scholar]
  • Thomas GR, Costelloe EA, Lunn DP, Stacey KJ, Delaney SJ, Passey R, McGlinn EC, McMorran BJ, Ahadizadeh A, Geczy CL, et al. G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. J Immunol. 2000 Apr 1;164(7):3870–3877. [PubMed] [Google Scholar]
  • Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5–10. [PubMed] [Google Scholar]
  • Schmidt AM, Yan SD, Yan SF, Stern DM. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 2001 Oct;108(7):949–955.[PMC free article] [PubMed] [Google Scholar]
  • Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol. 2001 Aug;159(2):513–525.[PMC free article] [PubMed] [Google Scholar]
  • Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ, Jr, Chow WS, Stern D, Schmidt AM. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 1998 Sep;4(9):1025–1031. [PubMed] [Google Scholar]
Department of Paediatrics, University of Muenster, Germany. ed.retsneum-inu@lleofd
Department of Paediatrics, University of Muenster, Germany. ed.retsneum-inu@lleofd
Copyright notice

Abstract

Methods: The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured.

Results: Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml).

Conclusions: S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.

Abstract
Full Text
Selected References
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.