mannose binding protein associated serine proteases

Summary

Summary: Serum serine proteases which participate in COMPLEMENT ACTIVATION. They are activated when complexed with the MANNOSE-BINDING LECTIN, therefore also known as Mannose-binding protein-Associated Serine Proteases (MASPs). They cleave COMPLEMENT C4 and COMPLEMENT C2 to form C4b2a, the CLASSICAL PATHWAY C3 CONVERTASE.

Top Publications

  1. Wallis R, Mitchell D, Schmid R, Schwaeble W, Keeble A. Paths reunited: Initiation of the classical and lectin pathways of complement activation. Immunobiology. 2010;215:1-11 pubmed publisher
    ..Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways. ..
  2. Zehnder A, Fisch U, Hirt A, Niggli F, Simon A, Ozsahin H, et al. Prognosis in pediatric hematologic malignancies is associated with serum concentration of mannose-binding lectin-associated serine protease-2 (MASP-2). Pediatr Blood Cancer. 2009;53:53-7 pubmed publisher
    ..Whether MASP-2 is an independent prognostic factor affecting risk stratification and anticancer therapy needs to be assessed in prospective, disease-specific studies. ..
  3. Hodge S, Matthews G, Dean M, Ahern J, Djukic M, Hodge G, et al. Therapeutic role for mannose-binding lectin in cigarette smoke-induced lung inflammation? Evidence from a murine model. Am J Respir Cell Mol Biol. 2010;42:235-42 pubmed publisher
    ..We provide evidence for Rac1/2/3 involvement in the MBL-mediated improvement in efferocytosis, and a rationale for investigating MBL as a supplement to existing therapies in smoking-related lung inflammation. ..
  4. Gal P, Dobó J, Zavodszky P, Sim R. Early complement proteases: C1r, C1s and MASPs. A structural insight into activation and functions. Mol Immunol. 2009;46:2745-52 pubmed publisher
    ..We also discuss some open questions and debated issues that need to be resolved in the future. ..
  5. Skjoedt M, Palarasah Y, Rasmussen K, Vitved L, Salomonsen J, Kliem A, et al. Two mannose-binding lectin homologues and an MBL-associated serine protease are expressed in the gut epithelia of the urochordate species Ciona intestinalis. Dev Comp Immunol. 2010;34:59-68 pubmed publisher
    ..In conclusion we present two urochordate MBLs and identify an associated serine protease, which support the concept of an evolutionary ancient origin of the lectin complement pathway...
  6. Megyeri M, Makó V, Beinrohr L, Doleschall Z, Prohaszka Z, Cervenak L, et al. Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function. J Immunol. 2009;183:3409-16 pubmed publisher
  7. St Swierzko A, Cedzynski M, Domzalska Popadiuk I, MacDonald S, Borkowska Klos M, Atkinson A, et al. Mannan-binding lectin-associated serine protease-2 (MASP-2) in a large cohort of neonates and its clinical associations. Mol Immunol. 2009;46:1696-701 pubmed publisher
    ..Moreover, no association of this SNP was apparent with prematurity, low birthweight or perinatal infections. ..
  8. de Rooij B, van Hoek B, ten Hove W, Roos A, Bouwman L, Schaapherder A, et al. Lectin complement pathway gene profile of donor and recipient determine the risk of bacterial infections after orthotopic liver transplantation. Hepatology. 2010;52:1100-10 pubmed publisher
    ..9 x 10(-8)), of which 80% was infection-related. Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. ..
  9. 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. ..

More Information

Publications38

  1. Skjoedt M, Hummelshoj T, Palarasah Y, Honore C, Koch C, Skjodt K, et al. A novel mannose-binding lectin/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation. J Biol Chem. 2010;285:8234-43 pubmed publisher
    ..It is found in complex with MBL and ficolins and may function as a potent inhibitor of the complement system in vivo. ..
  2. Degn S, Hansen A, Steffensen R, Jacobsen C, Jensenius J, Thiel S. MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation. J Immunol. 2009;183:7371-8 pubmed publisher
    ..MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system. ..
  3. Valles X, Sarrias M, Casals F, Farnós M, Piner R, Suarez B, et al. Genetic and structural analysis of MBL2 and MASP2 polymorphisms in south-eastern African children. Tissue Antigens. 2009;74:298-307 pubmed publisher
    ..7%) and P111L (25.4%)] were compared with those of two previously reported variants (R103C and D105G). None of the analysed MASP2 variants, with the exception of D105G, interfered with interactions with either MBL or ficolins (H and L). ..
  4. Liu J, Cao C, Ma Q. [Study on interaction between SARS-CoV N and MAP19]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2009;25:777-9 pubmed
    ..SARS-CoV N greatly increased the amount of MAP19. SARS-CoV N can bind with MAP19 in cells. Our study may be conductive to further research into the molecular mechanism of action between SARS-CoV N and MAP19. ..
  5. Kang J, Koo S, Kwon K, Park J, Kim J. Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2-q29 in squamous cell carcinoma of the lung. BMC Cancer. 2009;9:237 pubmed publisher
  6. Ip W, Takahashi K, Ezekowitz R, Stuart L. Mannose-binding lectin and innate immunity. Immunol Rev. 2009;230:9-21 pubmed publisher
    ..In this review we discuss both the attributes of MBL that make it a unique soluble pattern recognition molecule and also highlight its broader role in coordinating innate immune activation. ..
  7. Kaunisto M, Sjölind L, Sallinen R, Pettersson Fernholm K, Saraheimo M, Fröjdö S, et al. Elevated MBL concentrations are not an indication of association between the MBL2 gene and type 1 diabetes or diabetic nephropathy. Diabetes. 2009;58:1710-4 pubmed publisher
    ..Although most of the MBL2 SNPs studied were associated with the MBL concentration, no common variations (neither single SNPs nor their haplotype combinations) confer risk of type 1 diabetes or diabetic nephropathy. ..
  8. Takahashi M, Ishida Y, Iwaki D, Kanno K, Suzuki T, Endo Y, et al. Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. J Exp Med. 2010;207:29-37 pubmed publisher
    ..Thus, it is clear that MASP-1 is an essential protease of both the lectin and alternative complement pathways...
  9. Duus K, Thielens N, Lacroix M, Tacnet P, Frachet P, Holmskov U, et al. CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site. FEBS J. 2010;277:4956-64 pubmed publisher
    ..These findings demonstrate that MBL and L-ficolin interact with CD91, strongly suggesting that they have the potential to function as soluble recognition molecules for scavenging microbial and apoptotic material by CD91. ..
  10. Banda N, Takahashi M, Levitt B, Glogowska M, Nicholas J, Takahashi K, et al. Essential role of complement mannose-binding lectin-associated serine proteases-1/3 in the murine collagen antibody-induced model of inflammatory arthritis. J Immunol. 2010;185:5598-606 pubmed publisher
  11. Zuo D, Cai X, Zhao N, Zhang L, Chen Z. Location of MBL-associated serine proteases binding motifs on human mannan-binding lectin (MBL). Protein Pept Lett. 2010;17:131-6 pubmed
  12. Xing G, Chen M, Liu G, Zheng X, E J, Zhao M. Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis. J Clin Immunol. 2010;30:144-56 pubmed publisher
    ..Complement activation was involved in renal damage of human ANCA-negative pauci-immune CrGN but with heterogeneous activation pathways. Positive staining of C4d and MBL might be associated with poor renal outcome. ..
  13. Brouwer N, Frakking F, van de Wetering M, van Houdt M, Hart M, Budde I, et al. Mannose-binding lectin (MBL) substitution: recovery of opsonic function in vivo lags behind MBL serum levels. J Immunol. 2009;183:3496-504 pubmed publisher
  14. Yang Y, Xu X, Wang X, Zhu G. [Species and characteristics of protein adsorption on reused hemodialysis membranes]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2009;26:67-71 pubmed
    ..These proteins are in close relationship with human immune system; moreover, they are of great significance to the clinical mechanism for cleaning reuse hemodialyzers and to the development of new hemodialysis materials. ..
  15. Hansen S, Selman L, Palaniyar N, Ziegler K, Brandt J, Kliem A, et al. Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity. J Immunol. 2010;185:6096-104 pubmed publisher
  16. Cedzynski M, Atkinson A, St Swierzko A, MacDonald S, Szala A, Zeman K, et al. L-ficolin (ficolin-2) insufficiency is associated with combined allergic and infectious respiratory disease in children. Mol Immunol. 2009;47:415-9 pubmed publisher
    ..MBL insufficiency and MASP-2 deficiency are risk factors for recurrence of infections independently of allergic disease. ..
  17. Venkatraman Girija U, Furze C, Toth J, Schwaeble W, Mitchell D, Keeble A, et al. Engineering novel complement activity into a pulmonary surfactant protein. J Biol Chem. 2010;285:10546-52 pubmed publisher
    ..Thus, the active rather than the zymogen state is default in lectin.MASP complexes and must be inhibited through additional regions in circulating MBLs until triggered by pathogen recognition. ..
  18. Smithson A, Perello R, Aibar J, Espinosa G, Tassies D, Freire C, et al. Genotypes coding for low serum levels of mannose-binding lectin are underrepresented among individuals suffering from noninfectious systemic inflammatory response syndrome. Clin Vaccine Immunol. 2010;17:447-53 pubmed publisher
    ..The presence of high-MBL-producing genotypes in patients with a noninfectious insult is a risk factor for SIRS and ICU admission. ..
  19. Carroll M, Lack N, Sim E, Krarup A, Sim R. Multiple routes of complement activation by Mycobacterium bovis BCG. Mol Immunol. 2009;46:3367-78 pubmed publisher
    ..No M. bovis BCG cell surface or secreted protease appears likely to influence complement activation. Together, these data provide a more detailed analysis of the mechanisms by which M. bovis BCG interacts with the complement system. ..
  20. Gulla K, Gupta K, Krarup A, Gal P, Schwaeble W, Sim R, et al. Activation of mannan-binding lectin-associated serine proteases leads to generation of a fibrin clot. Immunology. 2010;129:482-95 pubmed publisher
    ..Additionally, MASP-catalysed deposition and polymerization of fibrin on the surface of micro-organisms may be protective by limiting the dissemination of infection. ..
  21. Wang Y, Yan J, Shi Y, Li P, Liu C, Ma Q, et al. Lack of association between polymorphisms of MASP2 and susceptibility to SARS coronavirus infection. BMC Infect Dis. 2009;9:51 pubmed publisher
    ..Our data do not suggest a role for MASP2 polymorphisms in SARS susceptibility in northern and southern China. ..
  22. Dobó J, Harmat V, Beinrohr L, Sebestyén E, Zavodszky P, Gal P. MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity. J Immunol. 2009;183:1207-14 pubmed publisher
    ..The structure shows that its substrate binding groove is accessible; however, its reactivity could be modulated by an unusually large 60-loop and an internal salt bridge involving the S1 Asp. ..
  23. Zuraw B, Christiansen S. Pathogenesis and laboratory diagnosis of hereditary angioedema. Allergy Asthma Proc. 2009;30:487-92 pubmed publisher
    ..The knowledge gained concerning the underlying mechanisms of the different types of HAE allow the clinician to approach the laboratory diagnosis with confidence and provides opportunities for novel therapeutic strategies. ..
  24. Cestari I, Krarup A, Sim R, Inal J, Ramirez M. Role of early lectin pathway activation in the complement-mediated killing of Trypanosoma cruzi. Mol Immunol. 2009;47:426-37 pubmed publisher
    ..Our findings establish that the complement lectin pathway recognizes T. cruzi and provide molecular insights into how the infectious stage inhibits this activation to resist complement system killing. ..
  25. Matsushita M. Ficolins: complement-activating lectins involved in innate immunity. J Innate Immun. 2010;2:24-32 pubmed publisher
    ..Thus, serum ficolins play an important role in innate immunity. ..
  26. Xu X, Yang Y, Zhu N. Characteristics and molecular mechanism of adhesion proteins on reused hemodialysis membranes. Blood Purif. 2009;27:321-9 pubmed publisher
    ..56 +/- 1.36, p < 0.01). The dipole moment of a polysulfone membrane molecule has a tendency to absorb molecules with a negative charge. These results are of significance in understanding and improving membrane protein interactions. ..
  27. Degn S, Jensen L, Gal P, Dobó J, Holmvad S, Jensenius J, et al. Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene involved in regulation of the complement system. J Immunol Methods. 2010;361:37-50 pubmed publisher
    ..Thus, neither of the two proteins behaves as a classical acute phase protein. ..
  28. Kocsis A, Kekesi K, Szasz R, Végh B, Balczer J, Dobó J, et al. Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose-binding lectin-associated serine protease (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation. J Immunol. 2010;185:4169-78 pubmed publisher
    ..Because the lectin pathway has been implicated in several life-threatening pathological states, these inhibitors should be considered as lead compounds toward developing lectin pathway blocking therapeutics. ..
  29. Gulla K, Gupta K, Hajela K. Functional estimation of mannose binding lectin associated serine protease (MBL-MASPs) in human serum. Indian J Med Res. 2009;130:428-32 pubmed
    ..Our findings showed that the method developed for the estimation of functional MBL-MASPs levels in human serum is simple, cost-effective and comparable with existing ELISA method. ..