Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis.

Abstract

As a potent effector of innate immunity, the complement system has been shown to be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the role of the membrane attack complex (MAC) in the development of IBD is still largely unknown. Here, we used C6-deficient mice in which MAC formation was blocked due to the absence of C6 to develop an acute colitis model by the administration of dextran sulfate sodium (DSS). The results showed that DSS-induced colitis was aggravated in C6-deficient mice compared with wild-type (WT) mice, as represented by the markedly greater weight loss, higher disease activity index (DAI), shortened colon length, more severe histological injury with increased epithelial ulcerations, and massively increased infiltration of leukocytes accompanied by much higher myeloperoxidase (MPO) levels in local inflammatory colonic sites. In addition, the DSS-induced colitis in C6-deficient mice could be significantly ameliorated by the exogenous C6 from WT sera. Furthermore, the significantly enhanced production of pro-inflammatory mediators, including IL-1β, IL-6, CXCL-1, CCL-3, TGF-β1 and IL-17F, was also observed in C6-deficient mice. Unexpectedly, the aggravated colitis in C6-deficient mice may be not due to the increase of lipopolysaccharide (LPS) levels in serum. Overall, we demonstrated that MAC exerts a protective role in acute colitis, strongly highlighting the host defense function of the complement system.

• Authors: Peipei Ding, Ling Li, Tianbao Huang, Chaoqun Yang, Enjie Xu, Na Wang, Long Zhang, Hongyu Gu, Xudong Yao, Xuhui Zhou, Weiguo Hu
• Journal: Immunobiology (Immunobiology) Vol. 221 Issue 11 Pg. 1293-303 (11 2016) ISSN: 1878-3279 [Electronic] Netherlands
• PMID: 27316715 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical References

• Complement C6
• Complement Membrane Attack Complex
• Cytokines
• Inflammation Mediators
• Complement System Proteins
• Dextran Sulfate

Topics

• Animals
• Colitis (drug therapy, etiology, metabolism, pathology)
• Complement C6 (administration & dosage, deficiency, immunology)
• Complement Membrane Attack Complex (immunology, metabolism)
• Complement System Proteins (immunology, metabolism)
• Cytokines (metabolism)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• Disease Susceptibility
• Hereditary Complement Deficiency Diseases
• Humans
• Immunologic Deficiency Syndromes (complications, immunology)
• Inflammation Mediators (metabolism)
• Inflammatory Bowel Diseases (immunology, metabolism, pathology)
• Intestinal Mucosa (immunology, metabolism, pathology)
• Leukocytes (immunology, metabolism, pathology)
• Mice
• Mice, Knockout