Detection of complement C3 and factor B gene expression in normal colorectal mucosa, adenomas and carcinomas

Abstract

SUMMARYLocal secretion of complement components in the human intestine has been previously reported. However, the cellular source has not been identified. In this study, we demonstrate complement C3 and factor B mRNA expression in the normal colonic mucosa by in situ hybridization analysis. C3 and factor B genes were found to be expressed at high levels in the epithelial cells of the lower parts of the crypts in colonic mucosa, and this expression decreased gradually from the crypt base to the luminal surface. At the upper crypt and the luminal surface, these genes almost disappeared. C3 and factor B genes were expressed in all crypts at the same level. Furthermore, C3 and factor B gene expression was also identified in adenomas and carcinomas. In these neoplastic tissues, C3 and factor B genes were expressed uniformly, and the polarized distribution observed in the normal crypts was not detected. It is likely that complement components are locally synthesized in the intestine, and that these complement components may actively participate in normal immune and inflammatory responses over the enormous surface area of the intestinal mucosa.

Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer

“…20,31 In papillary thyroid cancer, however, we found no evidence for local complement production, as only the protein of C3c without its corresponding mRNA transcript was detected. This indicates that the presence of these complement proteins was not due to local production, but the result of deposition from the serum and in situ activation.…”

“…PCR primers for human C3 gene were 5 0 -TCGGATGACAAGGTCACCCT-3 0 (sense), 5 0 -GACAACCATGCTCTCGGTGAA-3 0 (antisense). 20 The 407-bp size product was extracted from gel using gel extraction kit (Qiagen, Hilden, Germany) and ligated into a pGM-T vector (Tiangen Biotech, Beijing, China). Plasmid was extracted by Tiangen Tianperp Mini Plasmid kit.…”

“…19 Complement protein mRNA synthesis has been demonstrated in colon adenomas and carcinomas. 20 In papillary thyroid cancer, C3d, C4d, C5, and C5b-C9 have been detected at the protein level, but it is currently unknown whether complement proteins are also produced by papillary thyroid cancer cells. 11,21 In cancer immunology, complement proteins are thought to contribute to antitumor immune surveillance.…”

Role of glycan synthesis in colonization of the mammalian gut by the bacterial symbiont Bacteroides fragilis

“…The synthesis of surface polysaccharides is correlated directly with the ability of many bacteria to resist the bactericidal effects of a particular innate immune factor, complement (17)(18)(19). Complement has been studied largely as a serum factor, but components of the complement cascade are synthesized by normal colonic epithelial cells (20,21) and may play a role in maintaining homeostasis in the gut. Based on the importance of surface polysaccharides of other bacteria in resisting complementmediated killing, we tested the ability of the acapsular strain to survive in the presence of complement.…”

The increased mucosal mRNA expressions of complement C3 and interleukin-17 in inflammatory bowel disease

“…Hepatocytes are the primary source of complement components that circulate through the bloodstream [24]. Conversely, it has been generally accepted that complements are produced locally and contribute to host defence in the tissue sites [24][25][26]. Because the intestinal mucosa is one of the tissues in which a large number of immune cells are resident, it is likely that the locally biosynthesized complements in the intestine might contribute to the immune and inflammatory responses of the intestinal mucosa via modulation of T cell responses.…”