scholarly journals Splenic RNA and MicroRNA Mimics Promote Complement Factor B Production and Alternative Pathway Activation via Innate Immune Signaling

2016 ◽  
Vol 196 (6) ◽  
pp. 2788-2798 ◽  
Author(s):  
Lin Zou ◽  
Yan Feng ◽  
Ganqiong Xu ◽  
Wenling Jian ◽  
Wei Chao
Keyword(s):  
Alternative Pathway ◽  
Innate Immune ◽  
Complement Factor ◽  
Immune Signaling ◽  
Factor B ◽  
Complement Factor B ◽  
Innate Immune Signaling ◽  
Pathway Activation

scholarly journals Complement Factor B Mediates Ocular Angiogenesis through Regulating the VEGF Signaling Pathway

2021 ◽  
Vol 22 (17) ◽  
pp. 9580
Author(s):  
Hannah Murray ◽  
Beiying Qiu ◽  
Sze Yuan Ho ◽  
Xiaomeng Wang
Keyword(s):  
Signaling Pathway ◽  
Alternative Pathway ◽  
Complement Factor ◽  
Dependent Manner ◽  
Factor B ◽  
Ocular Angiogenesis ◽  
Complement Factor B ◽  
Ocular Neovascularization ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the catalytic subunit of CFB (Bb), the enzymatic site for the cleavage of a new molecule of C3 into C3b. In addition to its role in activating the AP, CFB has been implicated in pathological ocular neovascularization, a common feature of several blinding eye diseases, however, with somewhat conflicting results. The focus of this study was to investigate the direct impact of CFB on ocular neovascularization in a tightly controlled environment. Using mouse models of laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), our study demonstrated an increase in CFB expression during pathological angiogenesis. Results from several in vitro and ex vivo functionality assays indicated a promoting effect of CFB in angiogenesis. Mechanistically, CFB exerts this pro-angiogenic effect by mediating the vascular endothelial growth factor (VEGF) signaling pathway. In summary, we demonstrate compelling evidence for the role of CFB in driving ocular angiogenesis in a VEGF-dependent manner. This work provides a framework for a more in-depth exploration of CFB-mediated effects in ocular angiogenesis in the future.

scholarly journals Coexistence of Closed and Open Conformations of Complement Factor B in the Alternative Pathway C3bB(Mg2+) Proconvertase

2009 ◽  
Vol 183 (11) ◽  
pp. 7347-7351 ◽  
Author(s):  
Eva Torreira ◽  
Agustín Tortajada ◽  
Tamara Montes ◽  
Santiago Rodríguez de Córdoba ◽  
Oscar Llorca
Keyword(s):  
Alternative Pathway ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

scholarly journals Chronic Innate Immune Signaling in Myelodysplasia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-33-SCI-33
Author(s):  
Daniel T. Starczynowski
Keyword(s):  
Conflicts Of Interest ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Inflammatory Factors ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Pathway Activation ◽  
A Cell ◽  
Immune Pathway ◽  
Open Question

Abstract Chronic inflammatory diseases associated with activated innate immune signaling pathways often precede Myelodysplastic Syndromes (MDS), thus a role for chronic innate immune signaling in hematopoietic cells is suspected in the development of MDS. The innate immune system recognizes pathogens and host cellular by-products by pattern recognition receptors (PRR). Among the first PRRs to be identified were the Toll-like receptors (TLRs), which consist of 10 human members. Upon binding to ligand, TLRs recruit intracellular adaptors, kinases, and effector molecules which results in pathway activation. Chronic TLR signaling impairs HSC function, creates an inflammatory environment, and alters normal hematopoiesis, which suggests a causal role in MDS. Despite growing evidence linking dysregulation of innate immune signaling in MDS, how sustained activation of innate immune signaling downstream of various receptor families contributes to MDS remains an open question. This talk will highlight the recent evidence that implicates a cell-intrinsic role of innate immune pathway activation in MDS HSC and environmental inflammatory factors that are involved in the pathogenesis of MDS. Disclosures No relevant conflicts of interest to declare.

scholarly journals Chronic immune response dysregulation in MDS pathogenesis

Blood ◽  
2018 ◽  
Vol 132 (15) ◽  
pp. 1553-1560 ◽  
Author(s):  
Laura Barreyro ◽  
Timothy M. Chlon ◽  
Daniel T. Starczynowski
Keyword(s):  
Immune Response ◽  
Innate Immune ◽  
Direct Role ◽  
Immune Signaling ◽  
Innate Immune Signaling ◽  
Pathway Activation ◽  
Immune Pathway ◽  
Innate Immune Pathway ◽  
Inflammatory Component

Abstract Chronic innate immune signaling in hematopoietic cells is widely described in myelodysplastic syndromes (MDS), and innate immune pathway activation, predominantly via pattern recognition receptors, increases the risk of developing MDS. An inflammatory component to MDS has been reported for many years, but only recently has evidence supported a more direct role of chronic innate immune signaling and associated inflammatory pathways in the pathogenesis of MDS. Here we review recent findings and discuss relevant questions related to chronic immune response dysregulation in MDS.

scholarly journals Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long H. Ngo ◽  
M. Austin Argentieri ◽  
Simon T. Dillon ◽  
Blake Victor Kent ◽  
Alka M. Kanaya ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Plasma Protein ◽  
Expression Profiles ◽  
South Asians ◽  
Predictive Biomarkers ◽  
Information Criteria ◽  
Blood Protein ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

AbstractBlood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.

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