Extrahepatic synthesis of complement proteins in inflammation

Laufer, J; Katz, Yitzhak; Passwell, J H

doi:10.1016/s0161-5890(01)00044-x

Cited by 74 publications

(48 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…C3 plays a central role in the complement cascade (15). Hepatocytes are the major source of the circulating or systemic pools of C3, although significant, but smaller, amounts are produced locally by cells of the immune system or by other cell types (23,24). The locally produced complement components contribute to the activation of APCs and T cells and drive CD4 + T cell differentiation, expansion, and survival (25)(26)(27).…”

Section: /2mentioning

confidence: 99%

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Ag-specific CD8+ T cell contraction (contraction), which occurs after the resolution of infection, is critical for homeostasis of the immune system. Although complement components regulate the primary CD8+ T cell response, there is insufficient evidence supporting their role in regulating contraction and memory. In this study, we show that C3-deficient (C3−/−) mice exhibited significantly less CD8+ T cell contraction than did wild-type mice postinfection with recombinant Listeria monocytogenes expressing OVA. Kinetic analyses also revealed decreased contraction in mice treated with cobra venom factor to deplete C3, which was consistent with the results in C3−/− recipient mice transplanted with bone marrow cells from the same donors as wild-type recipient mice. The phenotypes of memory cells generated by C3−/− mice were not altered compared with those of wild-type mice. Further, C5aR signaling downstream of C3 was not involved in the regulation of contraction. Moreover, the regulation of contraction by C3 may be independent of the duration of antigenic stimulation or the functional avidity of effector CD8+ T cells. However, reduced contraction in C3−/− mice was accompanied by a decrease in the proportion of KLRG-1hi (killer-cell lectin-like receptor G1) CD127lo short-lived effector cells at the peak of the response and correlated with a reduction in the levels of inflammatory cytokines, such as IL-12 and IFN-γ, produced early postinfection. These results provide new insights into the role of systemic C3 in regulating contraction following intracellular bacterial infection and may help to develop vaccines that are more effective.

show abstract

Section: /2mentioning

confidence: 99%

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Tan

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The liver is the main source of complement synthesis and the complement molecules constitute approximately 5% of the total serum proteins. Many extrahepatic cells such as monocytes, endothelial cells, epithelial cells, glial cells, and neurons also produce complements 12 presumably as part of a defence mechanism, though they can be counterproductive leading to local tissue damage. The multiple biological activities of this cascade include control of inflammatory reactions and chemotaxis, clearance of immune complexes, cellular activation and antimicrobial defence.…”

Section: Introductionmentioning

confidence: 99%

The complement system and age-related macular degeneration

Sivaprasad

Chong

2006

Eye

View full text Add to dashboard Cite

Purpose Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. There are increasing evidences to suggest the complement system may play a significant role on the pathogenesis of AMD. In this review, we summarise the current research in this area. Methods Review of literature. Results The complement system is a complex system with several activation pathways. Complement factor H (CFH) polymorphisms has been associated with increase risk of AMD. CFH is an inhibitor protein; the polymorphisms might cause uncontrolled activation by initiation events. Conclusion Further studies on the molecular basis of the complement-mediated pathogenesis of AMD may offer novel therapy to AMD Eye (2006) 20, 867-872.

show abstract

“…Both direct and indirect effects of complement activation have been implicated as having roles in tissue injury associated with inflammatory diseases of gastrointestinal tract. 23,24 However, the contribution of complement activation products, especially C5a, to pathology of colitis remains largely unknown. In this study, complement activation in IBD patients and colitic mice was detected and the role of complement activation products C5a in IBD pathogenesis was investigated using neutralizing antibody to C5a.…”

mentioning

confidence: 99%

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Chen¹,

Yang

Gao

et al. 2011

Laboratory Investigation

View full text Add to dashboard Cite

Complement represents a chief component of innate immunity in host defense. However, excessive complement activation has been involved in the pathogenesis of inflammatory diseases. In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (À2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD. The inflammatory bowel diseases (IBDs) encompassing Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of gastrointestinal tract, characterized by dysfunction of mucosal T cells, abnormal cytokine production, cellular inflammation, and ultimately damage to the intestinal lining. 1 Although the etiology of IBD remains unknown, there is circumstantial evidence to link IBD to the mucosal immune system's failure to attenuate immunity to endogenous antigen. 1 In recent years, several animal IBD models have been developed. 2,3 Although the relationship of many of these models to human disease is imperfect, the hapten-induced model of colonic inflammation in which 2,4,6-trinitrobenzene sulfonic acid (TNBS) is delivered intrarectally to BALB/c mice displays human CD-like features, notably predominantly IL-12-driving Th1 activity of the mucosal CD4 þ T-cell population and transmural mononuclear inflammation. 3 More recently, a pathogenic role of IL-23, the cytokine sharing p40 subunits with IL-12, has been evidenced in the development of CD. 4 Deficiency of IL-23-specific subunits (p19) leads to failure of colitis induction in a T-cell transfer model. This effect is attributed to suppression of IL-17 production and Th17 differentiation in the colons. 5 The factors that initiate intestinal pathology of CD and elicit Th1/Th17 immune reaction, however, are still

show abstract

Extrahepatic synthesis of complement proteins in inflammation

Cited by 74 publications

References 74 publications

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

Systemic C3 Modulates CD8+ T Cell Contraction after Listeria monocytogenes Infection

The complement system and age-related macular degeneration

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Contact Info

Product

Resources

About