Lectin Complement Pathway in Emphysema.
Ontology highlight
ABSTRACT:
SUBMITTER: Serban KA
PROVIDER: S-EPMC6396862 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Publications
Lectin Complement Pathway in Emphysema.
Serban Karina A KA Mikosz Andrew A Strange Charlie C Janciauskiene Sabina M SM Stolk Jan J Jonigk Danny D Sandhaus Robert A RA Petrache Irina I
American journal of respiratory and critical care medicine 20190301 5
Similar Datasets
Project description:Dengue is a mosquito-borne viral disease causing significant health and economic burdens globally. The dengue virus (DENV) comprises four serotypes (DENV1-4). Usually, the primary infection is asymptomatic or causes mild dengue fever (DF), while secondary infections with a different serotype increase the risk of severe dengue disease (dengue hemorrhagic fever, DHF). Complement system activation induces inflammation and tissue injury, contributing to disease pathogenesis. However, in asymptomatic or primary infections, protective immunity largely results from the complement system's lectin pathway (LP), which is activated through foreign glycan recognition. Differences in N-glycans displayed on the DENV envelope membrane influence the lectin pattern recognition receptor (PRR) binding efficiency. The important PRR, mannan binding lectin (MBL), mediates DENV neutralization through (1) a complement activation-independent mechanism via direct MBL glycan recognition, thereby inhibiting DENV attachment to host target cells, or (2) a complement activation-dependent mechanism following the attachment of complement opsonins C3b and C4b to virion surfaces. The serum concentrations of lectin PRRs and their polymorphisms influence these LP activities. Conversely, to escape the LP attack and enhance the infectivity, DENV utilizes the secreted form of nonstructural protein 1 (sNS1) to counteract the MBL effects, thereby increasing viral survival and dissemination.
| S-EPMC8310334 | biostudies-literature
Project description:Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate residues present on various microorganisms. Thus, we hypothesized that collectin-11 could be a novel initiation molecule in the lectin pathway of complement. We can show that collectin-11 associates with all the known MBL-associated serine proteases (MASP-1, MASP-2 and MASP-3) as well as the lectin complement pathway regulator MAP-1. Furthermore, we found that complex formation between recombinant collectin-11 and recombinant MASP-2 on Candida albicans leads to deposition of C4b. Native collectin-11 in serum mediated complement activation and deposition of C4b and C3b, and formation of the terminal complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway in addition to MBL, ficolin-1, ficolin-2 and ficolin-3.
| S-EPMC6741501 | biostudies-literature
Project description:PurposeThe current study aimed to investigate in an Armenian population the levels of pattern recognition molecules (PRMs) of lectin complement pathway (LCP), MBL (mannan-binding lectin) and M-ficolin in plasma in ischemic stroke (IS), and the possible association of 11 single nucleotide polymorphisms (SNPs) in MBL2, FCN1 and FCN2 genes.Patients and methodsA total of 122 patients with IS and 150 control subjects were included in this study. Immunofluorometric assays (TRIFMAs) and real-time polymerase chain reactions with TaqMan probes were conducted.ResultsAccording to the results, the levels of M-ficolin in IS patients are significantly higher than in control subjects, and the MBL2 rs11003125 and rs12780112 SNPs, as well as MBL2 rs12780112*T and FCN1 rs10120023*T minor alleles (MAs) are negatively associated with the risk of IS. Further, MBL2 rs11003125 and rs1800450 SNPs and the carriage of their MAs, as well as FCN1 rs2989727 SNP and the carriage of FCN1 rs10120023*T MA significantly alter plasma MBL and M-ficolin levels in IS patients, respectively. Five common haplotypes in MBL2 gene and three common haplotypes in FCN1 and FCN2 genes were revealed, among which CGTC was negatively associated with IS and decreasing MBL plasma levels in IS.ConclusionIn conclusion, we suggest that LCP PRMs are associated with the risk of developing IS, and may also participate in pathological events leading to post-ischemic brain damage. This study emphasizes the important contribution of alterations of LCP PRMs on genomic and proteomic levels to the pathomechanisms of ischemic stroke, at least in an Armenian population.
| S-EPMC8544564 | biostudies-literature
Project description:BackgroundThis exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome.MethodsConcentrations of ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL) were analyzed in CSF and plasma from patients with SAH. Samples were collected daily from admission until day 9 (CSF; N_PATIENTS = 63, n_SAMPLES = 399) and day 8 (plasma; N_PATIENTS = 50, n_SAMPLES = 358), respectively. Twelve neurologically healthy patients undergoing spinal anesthesia and 12 healthy blood donors served as controls. The development of DCI during hospitalization and functional outcome at 3 months (modified Rankin Scale) were registered for patients.ResultsOn admission, CSF levels of all LCP initiators were increased in SAH patients compared with healthy controls. Levels declined gradually over days in patients; however, a biphasic course was observed for ficolin-1. Increased CSF levels of all LCP initiators were associated with a poor functional outcome in univariate analyses. This relationship persisted for ficolin-1 and MBL in multivariate analysis after adjustments for confounders (age, sex, clinical severity, distribution and amount of blood on CT-imaging) and multiple testing (1.87 ng/mL higher in average, 95% CI, 1.17 to 2.99 and 1.69 ng/mL higher in average, 95% CI, 1.09 to 2.63, respectively). In patients who developed DCI compared with those without DCI, CSF levels of ficolin-1 and MBL tended to increase slightly more over time (p_interaction = 0.021 and 0.033, respectively); however, no association was found after adjustments for confounders and multiple testing (p-adj_interaction = 0.086 and 0.098, respectively). Plasma ficolin-1 and ficolin-3 were lower in SAH patients compared with healthy controls on all days. DCI and functional outcome were not associated with LCP initiator levels in plasma.ConclusionPatients with SAH displayed elevated CSF levels of ficolin-1, ficolin-2, ficolin-3, and MBL. Increased CSF levels of ficolin-1 and MBL were associated with a poor functional outcome.Trial registrationThis study was a retrospective analysis of samples, which had been prospectively sampled and stored in a biobank. Registered at clinicaltrials.gov ( NCT01791257 , February 13, 2013, and NCT02320539 , December 19, 2014).
| S-EPMC7661172 | biostudies-literature
Project description:The complement system plays a crucial role in host defense against pathogen infections and in the recognition and removal of damaged or altered self-components. Complement system activation can be initiated by three different pathways—classical, alternative, and lectin pathways—resulting in a proteolytic cascade, which culminates in multiple biological processes including opsonization and phagocytosis of intruders, inflammation, cell lysis, and removal of immune complexes and apoptotic cells. Furthermore, it also functions as a link between the innate and adaptive immune responses. The lectin pathway (LP) activation is mediated by serine proteases, termed mannan-binding lectin (MBL)-associated serine proteases (MASPs), which are associated with the pattern recognition molecules (PRMs) that recognize carbohydrates or acetylated compounds on surfaces of pathogens or apoptotic cells. These result in the proteolysis of complement C2 and C4 generating C3 convertase (C4b2a), which carries forward the activation cascade of complements, culminating in the elimination of foreign molecules. This chapter presents an overview of the complement system focusing on the characterization of MASPs and its genes, as well as its functions in the immune response.
| S-EPMC7120406 | biostudies-literature
Project description:The complement system is activated cascadically via three distinct major routes: classical pathway (CP), alternative pathway (AP) or lectin pathway (LP). The unique factors associated with the latter are collectins (mannose-binding lectin, collectin-10, collectin-11), ficolins (ficolin-1, ficolin-2, ficolin-3) and proteins of the mannose-binding lectin-associated serine protease (MASP) family (MASP-1, MASP-2, MASP-3, MAp19, MAp44). Collectins and ficolins are both pattern-recognising molecules (PRM), reactive against pathogen-associated molecular patterns (PAMP) or danger-associated molecular patterns (DAMP). The MASP family proteins were first discovered as complexes with mannose-binding lectin (MBL) and therefore named MBL-associated serine proteases, but later, they were found to interact with ficolins, and later still, collectin-10 and collectin-11. As well as proteolytic enzymes (MASP-1, MASP-2, MASP-3), the group includes non-enzymatic factors (MAp19, MAp44). In this review, the association-specific factors of the lectin pathway with haematologic malignancies and related infections are discussed.
| S-EPMC7408476 | biostudies-literature
Project description:BACKGROUND:Mannose-binding lectin (MBL) and ficolins are pattern recognition molecules (PRMs) that play an important role during infection through activation of the lectin complement pathway. We assessed whether plasma PRM levels were associated with mortality in patients with necrotizing soft tissue infection (NSTI). METHODS:We conducted a prospective, observational study over 25 months involving 135 NSTI patients with a maximum follow-up of 2.7 years. Blood samples were taken upon admission. Non-infected patients served as controls. RESULTS:PRM levels were significantly lower compared with controls. A baseline Ficolin-2 level below the median was associated with mortality at the end of follow-up (p = 0.007). No significant association was found for MBL, Ficolin-1 and Ficolin-3. A Ficolin-2 level below the median had a negative predictive value of 0.94 for 28-day mortality, and a level below the optimal cut-off was independently associated with 28-day mortality when adjusted for age, sex and chronicity [hazard ratio 6.27 (95% confidence interval 2.28-17.21), p < 0.0001], also when Simplified Acute Physiology Score II was included in the analysis [hazard ratio 3.16 (95% confidence interval 1.03-9.73), p = 0.045]. CONCLUSIONS:All PRMs were significantly lower in patients with NSTI than in controls. Only baseline Ficolin-2 was associated with short- and long-term mortality. A high baseline Ficolin-2 level indicated a 94% chance of surviving the first 28 days after admission.
| S-EPMC6738884 | biostudies-literature
Project description:Salivary secretions from blood-feeding arthropods are rich in bioactive compounds that counteract blood clotting, platelet aggregation, complement activation, and vasoconstriction. Despite the identification and characterization of various salivary components in blood-feeding arthropods, their role in complement inhibition, particularly in black flies, remains underexplored. Here, we found that Guianensin, a salivary protein from Simulium guianense, is a specific inhibitor of the lectin pathway of the complement. Guianensin targets MASP-2, a serine protease crucial for LP activation resulting in reduced C4 and C5b-9 complex deposition. Guianensin also inhibits the procoagulant activity of MASP-2 in vitro. No interaction with C1s, C1r, or other downstream complement proteins was found. Using a lipopolysaccharide-induced murine lung injury model, Guianensin significantly reduced neutrophil numbers and inflammatory cytokines, demonstrating its strong anti-inflammatory activity in vivo. Guianensin emerges as a novel complement inhibitor and a potential candidate for therapeutic applications.
| S-EPMC11874034 | biostudies-literature
Project description:We explored the involvement of the lectin pathway of complement in post-traumatic brain injury (TBI) pathophysiology in humans. Brain samples were obtained from 28 patients who had undergone therapeutic contusion removal, within 12 h (early) or from >12 h until five days (late) from injury, and from five non-TBI patients. Imaging analysis indicated that lectin pathway initiator molecules (MBL, ficolin-1, ficolin-2 and ficolin-3), the key enzymes MASP-2 and MASP-3, and the downstream complement components (C3 fragments and TCC) were present inside and outside brain vessels in all contusions. Only ficolin-1 was found in the parenchyma of non-TBI tissues. Immunoassays in brain homogenates showed that MBL, ficolin-2 and ficolin-3 increased in TBI compared to non-TBI (2.0, 2.2 and 6.0-times) samples. MASP-2 increased with subarachnoid hemorrhage and abnormal pupil reactivity, two indicators of structural and functional damage. C3 fragments and TCC increased, respectively, by 3.5 - and 4.0-fold in TBI compared to non-TBI tissue and significantly correlated with MBL, ficolin-2, ficolin-3, MASP-2 and MASP-3 levels in the homogenates. In conclusion, we show for the first time the direct presence of lectin pathway components in human cerebral contusions and their association with injury severity, suggesting a central role for the lectin pathway in the post-traumatic pathophysiology of human TBI.
| S-EPMC6501516 | biostudies-literature
Project description:3MC syndrome has been proposed as a unifying term encompassing the overlapping Carnevale, Mingarelli, Malpuech and Michels syndromes. These rare autosomal recessive disorders exhibit a spectrum of developmental features, including characteristic facial dysmorphism, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. Here we studied 11 families with 3MC syndrome and identified two mutated genes, COLEC11 and MASP1, both of which encode proteins in the lectin complement pathway (collectin kidney 1 (CL-K1) and MASP-1 and MASP-3, respectively). CL-K1 is highly expressed in embryonic murine craniofacial cartilage, heart, bronchi, kidney and vertebral bodies. Zebrafish morphants for either gene develop pigmentary defects and severe craniofacial abnormalities. Finally, we show that CL-K1 serves as a guidance cue for neural crest cell migration. Together, these findings demonstrate a role for complement pathway factors in fundamental developmental processes and in the etiology of 3MC syndrome.
| S-EPMC3045628 | biostudies-literature