The Biological Functions of MBL-Associated Serine Proteases (MASPs)

Hajela, Krishnan; Kojima, Mayumi; Ambrus, Géza; Wong, Kah-Keng; Moffatt, Beryl E.; Ferluga, J.; Hajela, Sumati; Gál, Péter; Sim, Robert B.

doi:10.1078/0171-2985-00147

Cited by 141 publications

(118 citation statements)

References 39 publications

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“…Three separate MASPs plus two related proteins combine with MBL2 to form a complex or complexes similarly to C1r and C1s combining with C1q to initiate the classical pathway. 2,3 In humans, the MBL2 gene maps on chromosome 10q21.1 and encodes the MBL2 protein (248 amino acids) constituted by four domains: a short cysteine-rich N-terminal region (essential for oligomerization); a second large collagen-like domain; a short a-helical third domain and the C-terminal carbohydrate recognition domain. 4 Variant alleles disrupting the MBL2 molecule-or changing the amount of protein produced-are so often found in several populations that they can be considered like polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

Evolution of the mannose-binding lectin gene in primates

et al. 2004

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The mannose-binding lectin MBL2 plays an important role in the innate immune system. It binds carbohydrates surface, acts as an opsonin and activates the complement system. With the aim of studying the evolution of the MBL2 gene in primates, we sequenced its coding region in 12 non-human primate species and compared them with the human sequence. We demonstrated that nucleotide and amino-acidic sequences of the MBL2 among primates are highly homologous, underlining the importance of this molecule in the defense system against pathogen invasions. In particular, in the collagen-like domain that confers the characteristic structure to MBL2 protein, the identity among primates is really high. In the carbohydrate recognition domain, we evidenced some primates' group-specific amino-acidic mutations not resulting in changes of the structure or function of this MBL2 domain. Phylogenetic analysis did not evidence any positive selective pressure in MBL2 gene among non-human primates. Our findings indicate that MBL2 is well conserved in agreement with its important role in the immune system: in non-human primates, we did not observe the same 'plasticity' of the MBL2 human gene, where a frequency of more than 1% of nucleotide variations was described in the coding and promoter regions.

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Section: Introductionmentioning

confidence: 99%

Evolution of the mannose-binding lectin gene in primates

et al. 2004

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“…The MASPs are activated when MBL binds to a fitting carbohydrate pattern, resulting in cleavage of the polypeptide chains of the MASPs (49). The activated MASPs further cleave relevant substrates, i.e., C4 and C2 for MASP-2; C3 and C2 for MASP-1 (50). The activities of MASP-1 and MASP-2 can be regulated by C1-INH (51,52).…”

Section: Activation Of the Lectin Pathway By Natural Igm In A Modelmentioning

confidence: 99%

Activation of the Lectin Pathway by Natural IgM in a Model of Ischemia/Reperfusion Injury

Zhang

Takahashi

Alicot

et al. 2006

The Journal of Immunology

129

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Reperfusion of ischemic tissues elicits an acute inflammatory response involving serum complement, which is activated by circulating natural IgM specific to self-Ags exposed by ischemia. Recent reports demonstrating a role for the lectin pathway raise a question regarding the initial events in complement activation. To dissect the individual roles of natural IgM and lectin in activation of complement, mice bearing genetic deficiency in early complement, IgM, or mannan-binding lectin were characterized in a mesenteric model of ischemia reperfusion injury. 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.

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“…Recently, Hajela et al [19] suggested that MASP-1 is important in defense against spreading of infection due to fibrinogen and plasma transglutaminase (factor XIII) cleavage. Fibrinogen is a dimer of subunits built up of three chains: § , g and + of molecular masses of 67, 56 and 48 kDa, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Fibrinogen activation by PO25RP was tested according to the procedure described by Hajela et al [19]. Incubation of this substrate with PO25RP resulted in its cleavage in a dose-dependent manner (Fig.…”

Section: Activation Of Fibrinogen In Vitromentioning

confidence: 99%

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Role of the complement‐lectin pathway in anaphylactoid reaction induced with lipopolysaccharide in mice

et al. 2003

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We show that Proteus vulgaris O25 (PO25) lipopolysaccharide (LPS) induced an anaphylactoid reaction not only in wild-type and in lipid A non-responding mice but also in recombinase-activating gene-2-deficient (RAG-2 -/-) and in mast cell-deficient (W/Wv) animals. Western blot analysis indicated that PO25 LPS bound to Ra-reactive factor (RaRF), the complex of mannan-binding lectins (MBL) and MBL-associated serine proteases. Binding of RaRF to PO25 LPS led to the activation of C4 component without participation of either C1 or Ig, via the lectin pathway. Relative concentration of RaRF and hemolytic activity in mouse serum decreased rapidly during the process of anaphylactoid reaction. A significant drop of MBL-A, but not MBL-C level was observed. Administration with antiserum to RaRF prevented animals from death as a consequence of the inhibition of interaction of RaRF with the carbohydrate target and complement activation. These results indicate that complementlectin pathway activation is responsible for the anaphylactoid reaction induced with LPS in muramyldipeptide-primed mice. RaRF also activated fibrinogen in vitro suggesting the involvement of the coagulation system in the process investigated.

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The Biological Functions of MBL-Associated Serine Proteases (MASPs)

Cited by 141 publications

References 39 publications

Evolution of the mannose-binding lectin gene in primates

Evolution of the mannose-binding lectin gene in primates

Activation of the Lectin Pathway by Natural IgM in a Model of Ischemia/Reperfusion Injury

Role of the complement‐lectin pathway in anaphylactoid reaction induced with lipopolysaccharide in mice

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