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 (226.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Accurso F. J. Early pulmonary disease in cystic fibrosis. Curr Opin Pulm Med. 1997 Nov;3(6):400–403. doi: 10.1097/00063198-199711000-00002. [DOI] [PubMed] [Google Scholar]
- Boussac M., Garin J. Calcium-dependent secretion in human neutrophils: a proteomic approach. Electrophoresis. 2000 Feb;21(3):665–672. doi: 10.1002/(SICI)1522-2683(20000201)21:3<665::AID-ELPS665>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
- Clohessy P. A., Golden B. E. Elevated plasma levels of L1L and L1H in CF patients. Biochem Soc Trans. 1996 May;24(2):310S–310S. doi: 10.1042/bst024310s. [DOI] [PubMed] [Google Scholar]
- Cole A. M., Kim Y. H., Tahk S., Hong T., Weis P., Waring A. J., Ganz T. Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5–10. doi: 10.1016/s0014-5793(01)02731-4. [DOI] [PubMed] [Google Scholar]
- Dakin C., Henry R. L., Field P., Morton J. Defining an exacerbation of pulmonary disease in cystic fibrosis. Pediatr Pulmonol. 2001 Jun;31(6):436–442. doi: 10.1002/ppul.1072. [DOI] [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. doi: 10.1164/ajrccm.157.4.9704134. [DOI] [PubMed] [Google Scholar]
- Eichler I., Nilsson M., Rath R., Enander I., Venge P., Koller D. Y. Human neutrophil lipocalin, a highly specific marker for acute exacerbation in cystic fibrosis. Eur Respir J. 1999 Nov;14(5):1145–1149. doi: 10.1183/09031936.99.14511459. [DOI] [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. doi: 10.1007/BF01539138. [DOI] [PubMed] [Google Scholar]
- Frosch M., Strey A., Vogl T., Wulffraat N. M., 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. doi: 10.1002/1529-0131(200003)43:3<628::AID-ANR20>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
- Golden B. E., Clohessy P. A., Russell G., Fagerhol M. K. Calprotectin as a marker of inflammation in cystic fibrosis. Arch Dis Child. 1996 Feb;74(2):136–139. doi: 10.1136/adc.74.2.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goova M. T., Li J., Kislinger T., Qu W., Lu Y., Bucciarelli L. G., Nowygrod S., Wolf B. M., Caliste X., Yan S. F. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol. 2001 Aug;159(2):513–525. doi: 10.1016/S0002-9440(10)61723-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grasemann H., Ioannidis I., Tomkiewicz R. P., de Groot H., Rubin B. K., Ratjen F. Nitric oxide metabolites in cystic fibrosis lung disease. Arch Dis Child. 1998 Jan;78(1):49–53. doi: 10.1136/adc.78.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hofmann M. A., Drury S., Fu C., Qu W., Taguchi A., Lu Y., Avila C., Kambham N., Bierhaus A., Nawroth P. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999 Jun 25;97(7):889–901. doi: 10.1016/s0092-8674(00)80801-6. [DOI] [PubMed] [Google Scholar]
- Ilg E. C., Troxler H., Bürgisser D. M., Kuster T., Markert M., Guignard F., Hunziker P., Birchler N., Heizmann C. W. 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. doi: 10.1006/bbrc.1996.1144. [DOI] [PubMed] [Google Scholar]
- Karpati F., Hjelte F. L., 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. doi: 10.1080/00365540050164263. [DOI] [PubMed] [Google Scholar]
- Khan T. Z., Wagener J. S., Bost T., Martinez J., Accurso F. J., Riches D. W. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075–1082. doi: 10.1164/ajrccm/151.4.1075. [DOI] [PubMed] [Google Scholar]
- Koller D. Y., 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. doi: 10.1136/adc.75.6.498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kähler C. M., 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. doi: 10.1164/ajrccm.163.4.correspondence_b. [DOI] [PubMed] [Google Scholar]
- Lander H. M., Tauras J. M., Ogiste J. S., Hori O., Moss R. A., Schmidt A. M. 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. doi: 10.1074/jbc.272.28.17810. [DOI] [PubMed] [Google Scholar]
- Lügering N., Stoll R., Schmid K. W., 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. doi: 10.1111/j.1365-2362.1995.tb01982.x. [DOI] [PubMed] [Google Scholar]
- Nixon L. S., Yung B., Bell S. C., Elborn J. S., Shale D. J. Circulating immunoreactive interleukin-6 in cystic fibrosis. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1764–1769. doi: 10.1164/ajrccm.157.6.9704086. [DOI] [PubMed] [Google Scholar]
- Park L., Raman K. G., Lee K. J., Lu Y., Ferran L. J., Jr, Chow W. S., Stern D., Schmidt A. M. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 1998 Sep;4(9):1025–1031. doi: 10.1038/2012. [DOI] [PubMed] [Google Scholar]
- Robinson M. J., Hogg N. A comparison of human S100A12 with MRP-14 (S100A9). Biochem Biophys Res Commun. 2000 Sep 7;275(3):865–870. doi: 10.1006/bbrc.2000.3407. [DOI] [PubMed] [Google Scholar]
- Roth J., Goebeler M., Sorg C. S100A8 and S100A9 in inflammatory diseases. Lancet. 2001 Mar 31;357(9261):1041–1041. doi: 10.1016/S0140-6736(05)71610-X. [DOI] [PubMed] [Google Scholar]
- Schmidt A. M., Yan S. D., Yan S. F., Stern D. M. The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest. 2001 Oct;108(7):949–955. doi: 10.1172/JCI14002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith A. L., Redding G., Doershuk C., Goldmann D., Gore E., Hilman B., Marks M., Moss R., Ramsey B., Rubio T. Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis. J Pediatr. 1988 Apr;112(4):547–554. doi: 10.1016/s0022-3476(88)80165-3. [DOI] [PubMed] [Google Scholar]
- Thomas G. R., Costelloe E. A., Lunn D. P., Stacey K. J., Delaney S. J., Passey R., McGlinn E. C., McMorran B. J., Ahadizadeh A., Geczy C. L. G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. J Immunol. 2000 Apr 1;164(7):3870–3877. doi: 10.4049/jimmunol.164.7.3870. [DOI] [PubMed] [Google Scholar]
- Valletta E. A., 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. doi: 10.1111/j.1651-2227.1992.tb12209.x. [DOI] [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. doi: 10.1074/jbc.274.36.25291. [DOI] [PubMed] [Google Scholar]
- Watkin S. L., Elborn J. S., Cordon S. M., Hiller E. J., Shale D. J. 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. doi: 10.1002/ppul.1950170103. [DOI] [PubMed] [Google Scholar]
- Wolter J. M., Rodwell R. L., Bowler S. D., McCormack J. G. Cytokines and inflammatory mediators do not indicate acute infection in cystic fibrosis. Clin Diagn Lab Immunol. 1999 Mar;6(2):260–265. doi: 10.1128/cdli.6.2.260-265.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang Z., Tao T., Raftery M. J., Youssef P., Di Girolamo N., Geczy C. L. Proinflammatory properties of the human S100 protein S100A12. J Leukoc Biol. 2001 Jun;69(6):986–994. [PubMed] [Google Scholar]
- Yeh C. H., Sturgis L., Haidacher J., Zhang X. N., Sherwood S. J., Bjercke R. J., Juhasz O., Crow M. T., Tilton R. G., 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. doi: 10.2337/diabetes.50.6.1495. [DOI] [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. doi: 10.1006/prep.1998.0917. [DOI] [PubMed] [Google Scholar]