Genomes and Genes
Gene Symbol: Mbl1
Description: mannose-binding lectin (protein A) 1
Alias: MBL-A, MBP-A, S-MBP, mannose-binding protein A, mannan-binding protein, mannose binding lectin (A), mannose binding lectin, serum (A), ra-reactive factor polysaccharide-binding component p28B, raRF p28B
- Ip W, Takahashi K, Moore K, Stuart L, Ezekowitz R. Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med. 2008;205:169-81 pubmed publisher..Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways. ..
- Møller Kristensen M, Ip W, Shi L, Gowda L, Hamblin M, Thiel S, et al. Deficiency of mannose-binding lectin greatly increases susceptibility to postburn infection with Pseudomonas aeruginosa. J Immunol. 2006;176:1769-75 pubmed..aeruginosa infection following burn injury and suggests that MBL deficiency in humans maybe a premorbid variable in the predisposition to infection in burn victims. ..
- Held K, Thiel S, Loos M, Petry F. Increased susceptibility of complement factor B/C2 double knockout mice and mannan-binding lectin knockout mice to systemic infection with Candida albicans. Mol Immunol. 2008;45:3934-41 pubmed publisher..The more pronounced lack of complement activation in Bf/C2-/- mice leads to uncontrolled infection due to an opsonophagocytic defect. ..
- Takahashi K, Gordon J, Liu H, Sastry K, Epstein J, Motwani M, et al. Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis. Microbes Infect. 2002;4:773-84 pubmed..Our results indicate that MBL-A is a modulator of inflammation in vivo and in vitro in the mouse and that the role of MBL may extend beyond its role as an opsonin. ..
- Ruseva M, Kolev M, Dagnaes Hansen F, Hansen S, Takahashi K, Ezekowitz A, et al. Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment. Immunology. 2009;127:279-88 pubmed publisher..These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment. ..
- Sastry K, Zahedi K, Lelias J, Whitehead A, Ezekowitz R. Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. J Immunol. 1991;147:692-7 pubmed..The expression of both mannose-binding proteins A and C mRNA is restricted to the liver under basal and stress conditions. ..
- Holmskov U. Collectins and collectin receptors in innate immunity. APMIS Suppl. 2000;100:1-59 pubmed..The carbohydrate binding profile of CL-43 was analyzed by an inhibition assay with biotinylated CL-43, using solid-phase mannan as the ligand. (ABSTRACT TRUNCATED) ..
- Sastry R, Wang J, Brown D, Ezekowitz R, Tauber A, Sastry K. Characterization of murine mannose-binding protein genes Mbl1 and Mbl2 reveals features common to other collectin genes. Mamm Genome. 1995;6:103-10 pubmed..In this study, the two genes encoding MBP in mice--Mbl1 and Mbl2--have been isolated and their exon-intron structure studied to understand their evolutionary relationship ..
- Banda N, Takahashi M, Takahashi K, Stahl G, Hyatt S, Glogowska M, et al. Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement. Mol Immunol. 2011;49:281-9 pubmed publisher..We conclude that MASP-1 does not require binding to MBL-A, MBL-C, or FCN-A to activate the AP. MASP-1 may cleave pro-Df into mature Df through binding to FCN-B or to an unknown protein, or may function as an unbound soluble protein. ..
- Matthijsen R, de Winther M, Kuipers D, van der Made I, Weber C, Herias M, et al. Macrophage-specific expression of mannose-binding lectin controls atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 2009;119:2188-95 pubmed publisher..These results are the first to show that MBL is abundantly present and locally produced during early atherogenesis. Local MBL expression, by myeloid cells, is shown to critically control development of atherosclerotic lesions. ..
- Uemura K, Saka M, Nakagawa T, Kawasaki N, Thiel S, Jensenius J, et al. L-MBP is expressed in epithelial cells of mouse small intestine. J Immunol. 2002;169:6945-50 pubmed..These findings suggest that L-MBP plays a role in mucosal innate immunity. ..
- Hansen S, Thiel S, Willis A, Holmskov U, Jensenius J. Purification and characterization of two mannan-binding lectins from mouse serum. J Immunol. 2000;164:2610-8 pubmed..Serum concentrations of mMBL-A in laboratory strains and wild mice were found to vary from 5 to 80 microg/ml, with wild mice tending to show higher levels than laboratory strains. ..
- Møller Kristensen M, Hamblin M, Thiel S, Jensenius J, Takahashi K. Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice. J Invest Dermatol. 2007;127:1524-31 pubmed..Mice lacking C1q, C4, or C3 did not show the lack of eschar separation seen in MBL null-burn phenotype. These findings implicate MBL as an important molecule in the maintenance of the homeostatic balance. ..
- Takahashi K, Kurokawa K, Moyo P, Jung D, An J, Chigweshe L, et al. Intradermal immunization with wall teichoic acid (WTA) elicits and augments an anti-WTA IgG response that protects mice from methicillin-resistant Staphylococcus aureus infection independent of mannose-binding lectin status. PLoS ONE. 2013;8:e69739 pubmed publisher
- Cervera A, Planas A, Justicia C, Urra X, Jensenius J, Torres F, et al. Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PLoS ONE. 2010;5:e8433 pubmed publisher..In conclusion, genetically defined MBL-deficiency is associated with a better outcome after acute stroke in mice and humans. ..
- Pavlov V, Tan Y, McClure E, La Bonte L, Zou C, Gorsuch W, et al. Human mannose-binding lectin inhibitor prevents myocardial injury and arterial thrombogenesis in a novel animal model. Am J Pathol. 2015;185:347-55 pubmed publisher..We developed a novel mouse that expresses functional human mannose-binding lectin (MBL) 2 under the control of Mbl1 promoter...
- Pinto A, RAMOS H, Wu X, Aggarwal S, Shrestha B, Gorman M, et al. Deficient IFN signaling by myeloid cells leads to MAVS-dependent virus-induced sepsis. PLoS Pathog. 2014;10:e1004086 pubmed publisher..Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury. ..
- Stienstra R, Dijk W, van Beek L, Jansen H, Heemskerk M, Houtkooper R, et al. Mannose-binding lectin is required for the effective clearance of apoptotic cells by adipose tissue macrophages during obesity. Diabetes. 2014;63:4143-53 pubmed publisher..Finally, in humans, lower levels of circulating MBL were accompanied by enhanced macrophage influx in subcutaneous adipose tissue. We propose a novel role for MBL in the recognition and clearance of apoptotic adipocytes during obesity. ..
- Chan R, Ibrahim S, Takahashi K, Kwon E, McCormack M, Ezekowitz A, et al. The differing roles of the classical and mannose-binding lectin complement pathways in the events following skeletal muscle ischemia-reperfusion. J Immunol. 2006;177:8080-5 pubmed..Thus, the activation of both pathways is likely responsible for the full spectrum of injuries observed after skeletal muscle reperfusion injury. ..
- Østergaard J, Bjerre M, Ramachandrarao S, Sharma K, Nyengaard J, Hansen T, et al. Mannan-binding lectin in diabetic kidney disease: the impact of mouse genetics in a type 1 diabetes model. Exp Diabetes Res. 2012;2012:678381 pubmed publisher..Strain-specific MBL effects were found on downstream diabetic kidney changes. This emphasizes the importance of genetic background in this model of diabetic complications. ..
- Treadaway J, Zuo J. Mapping of the mouse glutamate receptor delta1 subunit (Grid1) to chromosome 14. Genomics. 1998;54:359-60 pubmed
- Hilfiker Kleiner D, Shukla P, Klein G, Schaefer A, Stapel B, Hoch M, et al. Continuous glycoprotein-130-mediated signal transducer and activator of transcription-3 activation promotes inflammation, left ventricular rupture, and adverse outcome in subacute myocardial infarction. Circulation. 2010;122:145-55 pubmed publisher
- Pavlov V, Skjoedt M, Siow Tan Y, Rosbjerg A, Garred P, Stahl G. Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. Circulation. 2012;126:2227-35 pubmed publisher..MAP-1 at pharmacological doses represents a novel therapeutic approach for human diseases involving the lectin pathway and its associated MASPs. ..
- Akiyama J, Volik S, Plajzer Frick I, Prince A, Sago H, Weier H, et al. Characterization of the mouse collectin gene locus. Am J Respir Cell Mol Biol. 1999;21:193-9 pubmed..found by polymerase chain reaction (PCR) to contain sequences from one of the mouse mannose-binding lectin genes (Mbl1). We used Southern mapping and subcloning of overlapping restriction fragments to characterize the gene locus...
- Zhang M, Takahashi K, Alicot E, Vorup Jensen T, Kessler B, Thiel S, et al. Activation of the lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol. 2006;177:4727-34 pubmed..The results reveal that IgM binds initially to ischemic Ag providing a binding site for mannan-binding lectin which subsequently leads to activation of complement and injury. ..
- Busche M, Walsh M, McMullen M, Guikema B, Stahl G. Mannose-binding lectin plays a critical role in myocardial ischaemia and reperfusion injury in a mouse model of diabetes. Diabetologia. 2008;51:1544-51 pubmed publisher..Further, the absence of MBL appears to inhibit hypertrophic remodelling and hyperglycaemia-induced loss of CPCs after just 2 weeks of hyperglycaemia in mice. ..
- de la Rosa X, Cervera A, Kristoffersen A, Valdés C, Varma H, Justicia C, et al. Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice. Stroke. 2014;45:1453-9 pubmed publisher..Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion. ..
- Ostergaard J, Bjerre M, Dagnaes Hansen F, Hansen T, Thiel S, Flyvbjerg A. Diabetes-induced changes in mannan-binding lectin levels and complement activation in a mouse model of type 1 diabetes. Scand J Immunol. 2013;77:187-94 pubmed publisher..Our findings support the previous clinical observations of increased MBL in type 1 diabetes. This change may be explained by alternations in both MBL production and turnover. ..
- Adamiak M, Abdelbaset Ismail A, Suszynska M, Abdel Latif A, Ratajczak J, Ratajczak M. Novel evidence that the mannan-binding lectin pathway of complement activation plays a pivotal role in triggering mobilization of hematopoietic stem/progenitor cells by activation of both the complement and coagulation cascades. Leukemia. 2017;31:262-265 pubmed publisher
- Endo Y, Nakazawa N, Iwaki D, Takahashi M, Matsushita M, Fujita T. Interactions of ficolin and mannose-binding lectin with fibrinogen/fibrin augment the lectin complement pathway. J Innate Immun. 2010;2:33-42 pubmed publisher..Therefore, it is suggested that the lectin pathway collaborates with the coagulation system in the first-line host defense against pathogens under conditions such as injury and inflammation. ..
- Banda N, Levitt B, Wood A, Takahashi K, Stahl G, Holers V, et al. Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generation in vitro. Clin Exp Immunol. 2010;159:100-8 pubmed publisher..We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP. ..
- Miwa T, Sato S, Gullipalli D, Nangaku M, Song W. Blocking properdin, the alternative pathway, and anaphylatoxin receptors ameliorates renal ischemia-reperfusion injury in decay-accelerating factor and CD59 double-knockout mice. J Immunol. 2013;190:3552-9 pubmed publisher..Further, they demonstrate a critical role for properdin and support its therapeutic targeting in renal IRI. ..
- Nimmerjahn F, Anthony R, Ravetch J. Agalactosylated IgG antibodies depend on cellular Fc receptors for in vivo activity. Proc Natl Acad Sci U S A. 2007;104:8433-7 pubmed..In contrast, the activity of these antibody glycovariants is fully dependent on the presence of activating Fc receptors. ..
- Mihai S, Chiriac M, Takahashi K, Thurman J, Holers V, Zillikens D, et al. The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita. J Immunol. 2007;178:6514-21 pubmed
- Pavlov V, La Bonte L, Baldwin W, Markiewski M, Lambris J, Stahl G. Absence of mannose-binding lectin prevents hyperglycemic cardiovascular complications. Am J Pathol. 2012;180:104-12 pubmed publisher..Together, these data suggest that MBL and the lectin complement pathway play a significant role in vascular dysfunction and cardiomyopathy after acute hyperglycemia. ..
- Choteau L, Parny M, FranÃ§ois N, Bertin B, Fumery M, Dubuquoy L, et al. Role of mannose-binding lectin in intestinal homeostasis and fungal elimination. Mucosal Immunol. 2016;9:767-76 pubmed publisher..This study shows that MBL expression is induced in the gut in response to C. albicans sensing and is required for intestinal homeostasis and host defense against C. albicans. ..
- Lawrence R, Carter T, Bell L, Else K, Summerfield J, Bickle Q. Altered antibody responses in mannose-binding lectin-A deficient mice do not affect Trichuris muris or Schistosoma mansoni infections. Parasite Immunol. 2009;31:104-9 pubmed publisher..These results suggest that MBL-A is not a necessary component for immunity to either T. muris or S. mansoni helminths, however, MBL-A appears to be necessary for the development of specific IgM responses to nematode antigens. ..
- Lutz C, Richards J, Scott K, Sinha S, Yang Feng T, Frankel W, et al. Neuropeptide Y receptor genes mapped in human and mouse: receptors with high affinity for pancreatic polypeptide are not clustered with receptors specific for neuropeptide Y and peptide YY. Genomics. 1997;46:287-90 pubmed..The physical association of these receptor genes correlates with ligand-binding properties, rather than sequence identity, and suggests a complex evolutionary relationship. ..
- Paerewijck O, Maertens B, Dreesen L, Van Meulder F, Peelaers I, Ratman D, et al. Interleukin-17 receptor A (IL-17RA) as a central regulator of the protective immune response against Giardia. Sci Rep. 2017;7:8520 pubmed publisher..Interestingly, the transcriptome data showed for the first time the involvement of the circadian clock in the host response following Giardia infection. ..
- Turner M. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today. 1996;17:532-40 pubmed
- Usui H, Ichikawa T, Kobayashi K, Kumanishi T. Cloning of a novel murine gene Sfmbt, Scm-related gene containing four mbt domains, structurally belonging to the Polycomb group of genes. Gene. 2000;248:127-35 pubmed..Northern blot analysis showed that the Sfmbt mRNAs were expressed most abundantly in the adult testis, and less intensively in all other tissues examined. ..
- Banda N, Takahashi K, Wood A, Holers V, Arend W. Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway. J Immunol. 2007;179:4101-9 pubmed..These results indicate that the alternative pathway amplification loop, with its ability to greatly enhance C3 activation, is necessary to mediate inflammatory arthritis induced by adherent immune complexes. ..
- Takahashi K, Chang W, Takahashi M, Pavlov V, Ishida Y, La Bonte L, et al. Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation. Immunobiology. 2011;216:96-102 pubmed publisher..Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. ..
- Rohrer B, Coughlin B, Kunchithapautham K, Long Q, Tomlinson S, Takahashi K, et al. The alternative pathway is required, but not alone sufficient, for retinal pathology in mouse laser-induced choroidal neovascularization. Mol Immunol. 2011;48:e1-8 pubmed publisher..Improving our understanding of the local regulation of this pathway in the eye is essential for developing improved treatment approaches for AMD. ..
- Zhou H, Yan H, Bertram P, Hu Y, Springer L, Thompson R, et al. Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation. Proc Natl Acad Sci U S A. 2013;110:E4335-44 pubmed publisher..Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA. ..
- Kuge S, Ihara S, Watanabe E, Watanabe M, Takishima K, Suga T, et al. cDNAs and deduced amino acid sequences of subunits in the binding component of mouse bactericidal factor, Ra-reactive factor: similarity to mannose-binding proteins. Biochemistry. 1992;31:6943-50 pubmed..Southern and Northern blotting analyses using these cDNAs indicated that the P28a and P28b polypeptides are the products of two unique mouse genes which are expressed in hepatic cells. ..
- Carter T, Sumiya M, Reilly K, Ahmed R, Sobieszczuk P, Summerfield J, et al. Mannose-binding lectin A-deficient mice have abrogated antigen-specific IgM responses and increased susceptibility to a nematode infection. J Immunol. 2007;178:5116-23 pubmed
- Ali Y, Lynch N, Haleem K, Fujita T, Endo Y, Hansen S, et al. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathog. 2012;8:e1002793 pubmed publisher..This study corroborates the essential function of MASP-2 in the lectin pathway and highlights the importance of MBL-independent lectin pathway activation in the host defense against pneumococci. ..
- Gonzalez S, Lukacs Kornek V, Kuligowski M, Pitcher L, Degn S, Kim Y, et al. Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes. Nat Immunol. 2010;11:427-34 pubmed publisher..Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination. ..
- Bidula S, Kenawy H, Ali Y, Sexton D, Schwaeble W, Schelenz S. Role of ficolin-A and lectin complement pathway in the innate defense against pathogenic Aspergillus species. Infect Immun. 2013;81:1730-40 pubmed publisher..However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A. ..
- Rokade S, Madan T. Testicular expression of SP-A, SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide. Immunobiology. 2016;221:975-85 pubmed publisher..Positive regulation of collectins by testosterone and their modulation in response to inflammation implicates their involvement in testicular immune-privilege. ..
- Petry F, Jakobi V, Wagner S, Tessema T, Thiel S, Loos M. Binding and activation of human and mouse complement by Cryptosporidium parvum (Apicomplexa) and susceptibility of C1q- and MBL-deficient mice to infection. Mol Immunol. 2008;45:3392-400 pubmed publisher..The contribution of the complement system and the lectin pathway in particular to the host defence against cryptosporidiosis may become apparent in situations of immunodeficiency such as HIV infections or in early childhood. ..
- Rothfuchs A, Roffe E, Gibson A, Cheever A, Ezekowitz R, Takahashi K, et al. Mannose-binding lectin regulates host resistance and pathology during experimental infection with Trypanosoma cruzi. PLoS ONE. 2012;7:e47835 pubmed publisher..These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. ..
- Yager P, You Z, Qin T, Kim H, Takahashi K, EZEKOWITZ A, et al. Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. J Cereb Blood Flow Metab. 2008;28:1030-9 pubmed publisher..was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI...
- White R, Dowler L, Adkison L, Ezekowitz R, Sastry K. The murine mannose-binding protein genes (Mbl 1 and Mbl 2) localize to chromosomes 14 and 19. Mamm Genome. 1994;5:807-9 pubmed
- La Bonte L, Pavlov V, Tan Y, Takahashi K, Takahashi M, Banda N, et al. Mannose-binding lectin-associated serine protease-1 is a significant contributor to coagulation in a murine model of occlusive thrombosis. J Immunol. 2012;188:885-91 pubmed publisher..Taken together, these findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key role in thrombus formation in vitro and in vivo. ..
- Moulton E, Atkinson J, Buller R. Surviving mousepox infection requires the complement system. PLoS Pathog. 2008;4:e1000249 pubmed publisher..In summary, the complement system acts in the first few minutes, hours, and days to control this poxviral infection until the adaptive immune response can react, and loss of this system results in lethal infection...
- Renner B, Strassheim D, Amura C, Kulik L, Ljubanovic D, Glogowska M, et al. B cell subsets contribute to renal injury and renal protection after ischemia/reperfusion. J Immunol. 2010;185:4393-400 pubmed publisher..However, nonperitoneal B cells attenuate renal injury after I/R, possibly through the production of IL-10. ..
- Tenner A. Membrane receptors for soluble defense collagens. Curr Opin Immunol. 1999;11:34-41 pubmed
- MORRISON H, Frye J, Davis Gorman G, Funk J, McDonagh P, STAHL G, et al. The contribution of mannose binding lectin to reperfusion injury after ischemic stroke. Curr Neurovasc Res. 2011;8:52-63 pubmed
- Motwani M, White R, Guo N, Dowler L, Tauber A, Sastry K. Mouse surfactant protein-D. cDNA cloning, characterization, and gene localization to chromosome 14. J Immunol. 1995;155:5671-7 pubmed..The mouse SP-D gene (Sftp4) has been localized to chromosome 14 (to a region syntenic to human chromosome 10), closely linked to the genes for other collagenous lectins, mannose-binding protein-A (MbI1), and SP-A (Sftp1). ..
- Peace B, Toney Earley K, Collins M, Waltz S. Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer. Cancer Res. 2005;65:1285-93 pubmed..This effect may be mediated in part through the regulation of angiogenesis and through proliferative and cell survival pathways regulated by mitogen-activated protein kinase and AKT. ..