Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells.

Benzaquen, Laura R.; Nicholson‐Weller, Anne; Halperin, José A.

doi:10.1084/jem.179.3.985

Cited by 241 publications

(138 citation statements)

References 27 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…This glycation attenuates its capacity to inhibit MAC formation [38]. It has been shown that MAC formation happens on cells and can lead to the release of growth factors without effects on cell viability [39]. Immunohistochemical studies observed no normal CD59 in the areas with severe glomerulosclerotic tissue and pronounced MAC deposition in diabetic patients [40].…”

Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis An increasing amount of evidence indicates that mannose-binding lectin (MBL) plays a role in the development of diabetic nephropathy. The main objective of the study was to analyse whether MBL influences the effects of diabetes on the kidneys. Materials and methods In one group of wild-type mice and in one group of MBL double knockout mice we induced diabetes by the use of streptozotocin as a model of type 1 diabetes. Two groups of non-diabetic mice, wild-type and MBL knockout, were also included. By two-way ANOVA we evaluated if MBL modulated the effects of diabetes by testing the interaction between diabetes and MBL. Results MBL interacted with the effects of diabetes on three outcome measures: kidney weight (p<0.001), urinary albumin excretion (p=0.001) and the expression of collagen IVα1 (Col4a1) mRNA (p=0.002). This means that the effects that diabetes normally has on these parameters were significantly modified by MBL. MBL showed a tendency to interact with the effects of diabetes on glomerular basement membrane thickness and total mesangial volume (p=0.065 and p=0.063, respectively). Glomerular volume and total mesangial volume were significantly smaller in animals lacking MBL than in wild-type animals (p=0.006 and p=0.047, respectively). Conclusions/interpretation These findings, for the first time, show that the degree of kidney alteration as a consequence of diabetes is modified by MBL. These findings support a pivotal role of MBL in the development of diabetic kidney disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

et al. 2007

View full text Add to dashboard Cite

show abstract

“…There are several lines of evidence that may explain the role of MAC in causing this excess cellularity. First, MAC has been shown to cause proliferation of glomerular mesangial, endothelial, and epithelial cells in vitro and therefore may be directly involved in inducing a increase in intrinsic cell number (17,21,44,45). Additionally, there are data indicating that MAC can induce the synthesis and/or secretion of a number of proinflammatory cytokines such as TNF-␣ and IL-1 (22,44), adhesion molecules such as ICAM-1 and E selectin (23), and chemokines such as IL-8 (46) and that these effects may play a role in the infiltration of cells to the glomerulus.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that sublethal MAC can mediate proliferative, proinflammatory and profibrotic effects in vitro in glomerular cells (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). MAC has also been shown to be involved in the pathogenesis of a number of glomerular diseases in vivo, including membranous nephropa-thy (24,25) and immune complex nephritis (26,27).…”

mentioning

confidence: 99%

CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice

Turnberg¹,

Botto²,

Warren³

et al. 2003

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Abstract. CD59 is a complement regulatory protein that inhibits the terminal part of the complement system, the membrane attack complex (MAC), a mediator of renal injury. Mice deficient in the Cd59a gene (mCd59aϪ/Ϫ) were used to investigate the role of CD59 in experimentally induced accelerated nephrotoxic nephritis, a model of immune complex-mediated glomerulonephritis. After accelerated nephrotoxic nephritis was induced by administration of sheep nephrotoxic globulin, mCd59aϪ/Ϫ mice and strain-matched controls on two genetic backgrounds, 129/Sv ϫ C57BL/6 and 129/Sv, were examined. For both, mCd59aϪ/Ϫ mice developed significantly greater glomerular cellularity than wild-type (WT) mice at day 5 after administration. At day 10 post-administration, mCd59aϪ/Ϫ mice exhibited more glomerular thrombosis than WT mice (thrombosis score, 1.8 [range, 1.4 to 4.0] versus 0.8 [range, 0.2 to 1.5] quadrants thrombosed per glomerulus, respectively; P ϭ 0.0006). In the majority of experiments, mCd59aϪ/Ϫ mice also had significantly more proteinuria than controls; however, there was no difference in serum creatinine or albumin. Quantitative immunofluorescence of kidney sections revealed significantly more C9 (as a marker of MAC) deposition within glomeruli of mCd59aϪ/Ϫ mice than WT controls (P Ͻ 0.001). There was no difference in deposition of C3 and sheep IgG between the two experimental groups. The lack of CD59a, by allowing unregulated MAC deposition, exacerbates the renal injury in this model of immune complex-mediated glomerulonephritis.

show abstract

“…Further investigation into complement-mediated growth factor production has shown that endothelial cells release basic fibroblast growth factor and platelet-derived growth factor in response to MAC stimulation (71). These two mitogens are known to stimulate the cell cycle (51) and angiogenesis (72).…”

Section: Complement Sustains Tumorigenesismentioning

confidence: 99%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

220

249

View full text Add to dashboard Cite

Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

show abstract

Terminal complement proteins C5b-9 release basic fibroblast growth factor and platelet-derived growth factor from endothelial cells.

Cited by 241 publications

References 27 publications

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice

CD59a Deficiency Exacerbates Accelerated Nephrotoxic Nephritis in Mice

Cancer and the Complement Cascade

Contact Info

Product

Resources

About