New Insights into the Role of Ficolins in the Lectin Pathway of Innate Immunity

Endo, Yuichi; Matsushita, Misao; Fujita, Teizo

doi:10.1016/bs.ircmb.2015.01.003

Cited by 72 publications

(76 citation statements)

References 214 publications

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“…A large number of studies have shown that ficolins play an important role in innate immunity in vertebrates and invertebrates (Endo et al, 2015). BlastX search revealed that the snail ficolin (contig_7199) was more closely related to ficolins found in other animals than to fibrinogen-related proteins (FREP) or fibrinogen-related molecules (FREM) described in B. glabrata (Zhang et al, 2004, 2008).…”

Section: Discussionmentioning

confidence: 99%

Pathogen-associated molecular patterns activate expression of genes involved in cell proliferation, immunity and detoxification in the amebocyte-producing organ of the snail Biomphalaria glabrata

Zhang

Loker

Sullivan

2016

Developmental & Comparative Immunology

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The anterior pericardial wall of the snail Biomphalaria glabrata has been identified as a site of hemocyte production, hence has been named the amebocyte-producing organ (APO). A number of studies have shown that exogenous abiotic and biotic substances, including pathogen associated molecular patterns (PAMPs), are able to stimulate APO mitotic activity and/or enlarge its size, implying a role for the APO in innate immunity. The molecular mechanisms underlying such responses have not yet been explored, in part due to the difficulty in obtaining sufficient APO tissue for gene expression studies. By using a modified RNA extraction technique and microarray technology, we investigated transcriptomic responses of APOs dissected from snails at 24 hours post-injection with two bacterial PAMPs, lipopolysaccharide (LPS) and peptidoglycan (PGN), or with fucoidan (FCN), which may mimic fucosyl-rich glycan PAMPs on sporocysts of Schistosoma mansoni. Based upon the number of genes differentially expressed, LPS exhibited the strongest activity, relative to saline-injected controls. A concurrent activation of genes involved in cell proliferation, immune response and detoxification metabolism was observed. A gene encoding checkpoint 1 kinase, a key regulator of mitosis, was highly expressed after stimulation by LPS. Also, seven different aminoacyl-tRNA synthetases that play an essential role in protein synthesis were found to be highly expressed. In addition to stimulating genes involved in cell proliferation, the injected substances, especially LPS, also induced expression of a number of immune-related genes including arginase, peptidoglycan recognition protein short form, tumor necrosis factor receptor, ficolin, calmodulin, bacterial permeability increasing proteins and E3 ubiquitin-protein ligase. Importantly, significant up-regulation was observed in four GiMAP (GTPase of immunity-associated protein) genes, a result which provides the first evidence suggesting an immune role of GiMAP in protostome animals. Moreover, altered expression of genes encoding cytochrome P450, glutathione-S-transferase, multiple drug resistance protein as well as a large number of genes encoding enzymes associated with degradation and detoxification metabolism was elicited in response to the injected substances.

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Section: Discussionmentioning

confidence: 99%

Pathogen-associated molecular patterns activate expression of genes involved in cell proliferation, immunity and detoxification in the amebocyte-producing organ of the snail Biomphalaria glabrata

Zhang

Loker

Sullivan

2016

Developmental & Comparative Immunology

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“…In this study, we have identified a role for ficolins as cytokine modulators. In addition to the opsonizing activity, ficolins are known to activate the lectin pathway of complement via interaction with MBL-ficolin-associated serine proteases [12], a property they share with MBL. Consequently, one mechanism by which ficolins could increase the cytokine response is through activation of complement.…”

Section: Discussionmentioning

confidence: 99%

“…Ficolins are a family of soluble pattern-recognition receptors that activate the lectin pathway of complement similar to mannose-binding lectin (MBL) [12,13,14]. They comprise a collagen-like domain and a fibrinogen-like domain, of which the latter is involved in ligand recognition.…”

Section: Introductionmentioning

confidence: 99%

Ficolins Promote Fungal Clearance in vivo and Modulate the Inflammatory Cytokine Response in Host Defense against <b><i>Aspergillus fumigatus</i></b>

et al. 2016

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Aspergillus fumigatus is an opportunistic fungal pathogen that causes severe invasive infections in immunocompromised patients. Innate immunity plays a major role in protection against A. fumigatus. The ficolins are a family of soluble pattern recognition receptors that are capable of activating the lectin pathway of complement. Previous in vitro studies reported that ficolins bind to A. fumigatus, but their part in host defense against fungal infections in vivo is unknown. In this study, we used ficolin-deficient mice to investigate the role of ficolins during lung infection with A. fumigatus. Ficolin knockout mice showed significantly higher fungal loads in the lungs 24 h postinfection compared to wild-type mice. The delayed clearance of A. fumigatus in ficolin knockout mice could not be attributed to a compromised recruitment of inflammatory cells. However, it was revealed that ficolin knockout mice exhibited a decreased production of proinflammatory cytokines in the lungs compared to wild-type mice following A. fumigatus infection. The impaired clearance and cytokine production in ficolin knockout mice was independent of complement, as shown by equivalent levels of A. fumigatus-mediated complement activation in ficolin knockout mice and wild-type mice. In conclusion, this study demonstrates that ficolins are important in initial innate host defense against A. fumigatus infections in vivo.

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“…MBL and the ficolins are circulating recognition molecules binding to molecular structures on damaged host cells further activating the mannose‐binding serine proteases, MASP1 and MASP2 36. MBL is also an acute phase reactant,37 and altered levels of FCN1–3 are reported in various pathological conditions, either due to consumption or changed expression 38. The lower level of FCN2 in the patient population at inclusion compared with healthy controls is in line with a previous observation seen in STEMI patients35 and is suggested to reflect consumption in the early phase of the disease.…”

Section: Discussionmentioning

confidence: 99%

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

et al. 2018

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AimsHeart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.Methods and resultsThe LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention‐treated ST‐elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow‐up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non‐shock group (n = 52). Controls (n = 44) were age‐matched and sex‐matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b‐9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non‐shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b‐9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b‐9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM‐1 and sVCAM‐1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b‐9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).ConclusionsComplement activation discriminated cardiogenic shock from non‐shock in acute ST‐elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.

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New Insights into the Role of Ficolins in the Lectin Pathway of Innate Immunity

Cited by 72 publications

References 214 publications

Pathogen-associated molecular patterns activate expression of genes involved in cell proliferation, immunity and detoxification in the amebocyte-producing organ of the snail Biomphalaria glabrata

Pathogen-associated molecular patterns activate expression of genes involved in cell proliferation, immunity and detoxification in the amebocyte-producing organ of the snail Biomphalaria glabrata

Ficolins Promote Fungal Clearance in vivo and Modulate the Inflammatory Cytokine Response in Host Defense against <b><i>Aspergillus fumigatus</i></b>

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

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