Skip to main content

Advertisement

Log in

Expression of C1q Complement Component in Barrett’s Esophagus and Esophageal Adenocarcinoma

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Aims

C1q, an element of the first component of complement, is known to be expressed by interdigitating and follicular dendritic cells in the spleen, where it has been suggested that C1q is involved in capturing immune complexes. The present study investigated whether C1q is expressed in Barrett's esophagus and esophageal adenocarcinoma and, if so, whether its expression is associated with dendritic cells.

Material and Methods

Endoscopic biopsy or operative surgical specimens were obtained from 15 patients with Barrett's esophagus, 13 patients with esophageal adenocarcinoma and 12 patients whose biopsy specimens did not show the presence of specialized intestinal metaplasia or adenocarcinoma. Barrett's esophagus was diagnosed by the presence of a macroscopic area of columnar-lined esophagus as well as microscopic intestinal metaplasia with goblet cells. Immunohistochemistry utilizing anti-C1q and markers for dendritic cells and macrophages was performed on sections of tissue samples embedded in paraffin. Double immunostaining with C1q/CD83 and C1q/CD68 was used to analyze the possible co-localization of C1q with dendritic cells and macrophages. The expression of C1q by dendritic cells and macrophages was also examined in in vitro studies using reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting.

Results

In all specimens studied, C1q expression was detected as being distributed irregularly throughout the lamina propria. A computerized quantitative analysis showed that C1q expression was significantly higher in tissue specimens without specialized intestinal-type metaplasia than in Barrett's esophagus specimens and specimens with adenocarcinoma. Double immunostaining revealed that dendritic cells and macrophages expressed C1q in all analyzed esophageal specimens. The expression of C1q by dendritic cells and macrophages was also demonstrated in in vitro studies using RT-PCR and Western blotting.

Conclusion

The findings suggest that reduced levels of the expression of C1q by dendritic cells and macrophages in the esophagus may play a role in the formation of immune responses associated with the formation of specialized intestinal metaplasia and the development of adenocarcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. O'Byrne KJ, Dalgleish AG. Chronic immune activation and inflammation as the cause of malignancy. Br J Cancer 2001;85:473–483.

    Article  PubMed  Google Scholar 

  2. Macarthur M, Hold GL, El-Omar EM. Inflammation and Cancer II. Role of chronic inflammation and cytokine gene polymorphisms in the pathogenesis of gastrointestinal malignancy. Am J Physiol Gastrointest Liver Physiol 2004;286:G515–520.

    Article  CAS  PubMed  Google Scholar 

  3. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature 2008;454:436–444.

    Article  CAS  PubMed  Google Scholar 

  4. Oberg S, Peters JH, DeMeester TR, et al. Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. Ann Surg 1997;226:522–530.

    Article  CAS  PubMed  Google Scholar 

  5. Der R, Tsao-Wei DD, DeMeester T, et al. Carditis: a manifestation of gastroesophageal reflux disease. Am J Surg Pathol 2001;25:245–252.

    Article  CAS  PubMed  Google Scholar 

  6. Moons LM, Kusters JG, Bultman E, et al. Barrett's oesophagus is characterized by a predominantly humoral inflammatory response. J Pathol 2005;207:269-276.

    Article  CAS  PubMed  Google Scholar 

  7. Abdel-Latif MM, Duggan S, Reynolds JV et al. Inflammation and esophageal carcinogenesis. Curr Opin Pharmacol 2009;9:396–404.

    Article  CAS  PubMed  Google Scholar 

  8. Bobryshev YV, Tran D, Killingsworth MC et al. Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma. J Gastrointest Surg 2009;13:44–53.

    Article  PubMed  Google Scholar 

  9. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.

    Article  CAS  PubMed  Google Scholar 

  10. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature 2007;449;419–426.

    Article  CAS  PubMed  Google Scholar 

  11. van de Ven R, Scheffer GL, Scheper RJ, et al. The ABC of dendritic cell development and function. Trends Immunol 2009;30:421–429.

    Article  PubMed  Google Scholar 

  12. Lotze MT, Thomson AW, eds. Dendritic cells: Biology and Clinical Applications, 2nd edn. San Diego, CA: Academic Press, 2001.

    Google Scholar 

  13. Lipscomb MF, Masten BJ. Dendritic cells: immune regulators in health and disease. Physiol Rev 2002;82;97–130.

    CAS  PubMed  Google Scholar 

  14. van Kooten C, Fiore N, Trouw LA, Csomor E, Xu W, Castellano G, Daha MR, Gelderman KA. Complement production and regulation by dendritic cells: molecular switches between tolerance and immunity. Mol Immunol 2008;45:4064–4072.

    Article  PubMed  Google Scholar 

  15. Lu J, Wu X, Teh BK. The regulatory roles of C1q. Immunobiology 2007;212:245–252.

    Article  CAS  PubMed  Google Scholar 

  16. Lu JH, Teh BK, Wang L, Wang YN, Tan YS, Lai MC, Reid KB. The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol 2008;5:9–21.

    Article  CAS  PubMed  Google Scholar 

  17. Schwaeble W, Schafer M.K, Petry F, et al. Follicular dendritic cells, interdigitating cells, and cells of the monocyte-macrophage lineage are the C1q-producing sources in the spleen. Identification of specific cell types by in situ hybridization and immunohistochemical analysis. J Immunol 1995;155:4971–4978.

    CAS  PubMed  Google Scholar 

  18. Cook HT, Botto M. Mechanisms of Disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nat Clin Pract Rheumatol 2006;2:330–337.

    Article  CAS  PubMed  Google Scholar 

  19. Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity 2007;40:560–566.

    Article  CAS  PubMed  Google Scholar 

  20. Lindau D, Decker P. Nph, DC and chromatin-mediated pathogenesis in systemic lupus erythematosus. Autoimmunity 2009;42:254–256.

    Article  CAS  PubMed  Google Scholar 

  21. Lechmann M, Zinser E, Golka A, Steinkasserer A. Role of CD83 in the immunomodulation of dendritic cells. Int Arch Allergy Immunol 2002;129:113–118.

    Article  CAS  PubMed  Google Scholar 

  22. Engering A, Geijtenbeek TB, van Vliet SJ, et al.The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. J Immunol 2002;168:2118–2126.

    CAS  PubMed  Google Scholar 

  23. Cao W, Lee SH, Lu J. CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells. Biochem J 2005;385(Pt 1):85–93.

    CAS  PubMed  Google Scholar 

  24. Bobryshev YV, Cao W, Phoon MC, Tran D, Chow VT, Lord RS, Lu J. Detection of Chlamydophila pneumoniae in dendritic cells in atherosclerotic lesions. Atherosclerosis 2004;173:185–195.

    Article  CAS  PubMed  Google Scholar 

  25. Lu J, Zheng MH, Yan J, Chen YP, Pan JP. Effects of vasoactive intestinal peptide on phenotypic and functional maturation of dendritic cells. Int Immunopharmacol. 2008;8:1449–1454.

    Article  CAS  PubMed  Google Scholar 

  26. Kishore U, Reid K.B. C1q: structure, function, and receptors. Immunopharmacology 2000, 49:159–170.

    Article  CAS  PubMed  Google Scholar 

  27. Reid K.B, Colomb M, Petry F, Loos M. Complement component C1 and the collectins—first-line defense molecules in innate and acquired immunity. Trends Immunol 2002;23:115–117.

    Google Scholar 

  28. Botto M, Dell'Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, Loos M, Pandolfi PP, Walport MJ. Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 1998;19:56–569.

    Article  CAS  PubMed  Google Scholar 

  29. Botto M. C1q knock-out mice for the study of complement deficiency in autoimmune disease. Exp Clin Immunogenet 1998;15:231–234.

    Article  CAS  PubMed  Google Scholar 

  30. Schaller M, Bigler C, Danner D, Ditzel HJ, Trendelenburg M. Autoantibodies against C1q in systemic lupus erythematosus are antigen-driven. J Immunol 2009;183:8225–8231.

    Article  CAS  PubMed  Google Scholar 

  31. Kaisho T. Type I interferon production by nucleic acid-stimulated dendritic cells. Front Biosci 2008;13:6034-6042.

    Article  CAS  PubMed  Google Scholar 

  32. Finke D, Eloranta ML, Rönnblom L. Endogenous type I interferon inducers in autoimmune diseases. Autoimmunity 2009;42:349–352.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Cancer Institute of New South Wales and the St. Vincent's Clinic Foundation, Sydney, for financial support. We thank Dr. Dinh Tran for assistance with immunohistochemical staining.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuri V. Bobryshev.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bobryshev, Y.V., Lu, J. & Lord, R.V.N. Expression of C1q Complement Component in Barrett’s Esophagus and Esophageal Adenocarcinoma. J Gastrointest Surg 14, 1207–1213 (2010). https://doi.org/10.1007/s11605-010-1230-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-010-1230-y

Keywords

Navigation