The mannan-binding lectin pathway of complement activation: biology and disease association

Petersen, Steen V.; Thiel, Steffen; Jensenius, Jens Christian

doi:10.1016/s0161-5890(01)00038-4

Cited by 264 publications

(190 citation statements)

References 114 publications

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“…It is well confirmed that higher oligomeric structures are necessary for MBL in its complement activation [2,11,32,33,37,[43][44][45]. In the present study, the binding to MASP-1/3 and mannan was seen only with the largermolecular form of MBL but not with the smaller one, which was consistent with this description.…”

Section: Discussionsupporting

confidence: 92%

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Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

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Mannose-binding lectin (MBL) activates complement through MBL-associated serine proteases (MASP). A deficiency in MBL due to mutations at exon 1 of the human MBL gene is reported to cause vulnerability to infection. We examined sera of known MBL genotype by gel filtration and assessed their elution patterns using an ELISA for MBL and identified two MBL forms, a high-molecular-mass form and a lower-molecular-mass form. By the identification of either or both forms in individual sera, three types of patterns emerged: type 1 consisted of a high-molecular form; type 2, of a low-molecular form; and type 3, of both forms. Types 1, 2 and 3 corresponded, respectively, to a wild type (A/A), a homozygous mutation at codon 54 (B/B) and their heterozygote (A/B). One exception was a heterozygous LXPA/LYPB phenotype that exhibited the type-2 pattern. Binding to mannan and MASP-1/3 occurred exclusively with the high-molecular form. An apparent MBL deficiency does not in fact represent a deficiency in MBL molecules but rather the presence of circulating oligomeric mutant MBL with impaired function.

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Section: Discussionsupporting

confidence: 92%

“…It plays an important role in activation of complement in cooperation with MBL-associated serine protease (MASP)-1, MASP-2 and MASP-3 and works to exclude microorganisms in concert with phagocytic cells [1][2][3]. A deficiency in MBL can cause a vulnerability to infection [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

et al. 2003

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“…The lectin pathway is initiated by complexes of pattern recognition molecules MBL or L-, H-, and M-ficolins with MBL-associated serine proteases (MASPs) (Petersen et al, 2001;Endo et al, 2006). The MBL or any of the ficolins binds to carbohydrate structures presented by a wide range of pathogens and mediate complement activation via activation of MASP-2.…”

Section: Introductionmentioning

confidence: 99%

Complement genetics, deficiencies, and disease associations

Mayilyan

2012

Protein Cell

148

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The complement system is a key component of innate immunity. More than 45 genes encoding the proteins of complement components or their isotypes and subunits, receptors, and regulators have been discovered. These genes are distributed throughout different chromosomes, with 19 genes comprising three significant complement gene clusters in the human genome. Genetic deficiency of any early component of the classical pathway (C1q, C1r/s, C2, C4, and C3) is associated with autoimmune diseases due to the failure of clearance of immune complexes (IC) and apoptotic materials, and the impairment of normal humoral response. Deficiencies of mannan-binding lectin (MBL) and the early components of the alternative (factor D, properdin) and terminal pathways (from C3 onward components: C5, C6, C7, C8, C9) increase susceptibility to infections and their recurrence. While the association of MBL deficiency with a number of autoimmune and infectious disorders has been well established, the effects of the deficiency of other lectin pathway components (ficolins, MASPs) have been less extensively investigated due to our incomplete knowledge of the genetic background of such deficiencies and the functional activity of those components. For complement regulators and receptors, the consequences of their genetic deficiency vary depending on their specific involvement in the regulatory or signalling steps within the complement cascade and beyond. This article reviews current knowledge and concepts about the genetic load of complement component deficiencies and their association with diseases. An integrative presentation of genetic data with the latest updates provides a background to further investigations of the disease association investigations of the complement system from the perspective of systems biology and systems genetics.

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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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The mannan-binding lectin pathway of complement activation: biology and disease association

Cited by 264 publications

References 114 publications

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

Relationship between gene polymorphisms of mannose‐binding lectin (MBL) and two molecular forms of MBL

Complement genetics, deficiencies, and disease associations

Evolution of the mannose-binding lectin gene in primates

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