Mannan-binding lectin (MBL)-associated serine protease-1 (MASP-1), a serine protease associated with humoral pattern-recognition molecules: Normal and acute-phase levels in serum and stoichiometry of lectin pathway components

S. Thiel, L. Jensen, S. E. Degn, H. J. Nielsen, P. Gál, J. Dobó, J. C. Jensenius

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Abstract

The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood in complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of the MASPs occurs leading to activation of the complement system, an important component of the innate immune system. Three proteins are produced from the MASP1 gene: MASP-1 and MASP-3 and MAp44. We present an assay specific for MASP-1, which is based on inhibition of the binding of anti-MASP-1-specific antibody to MASP-1 domains coated onto microtitre wells. MASP-1 was found in serum in large complexes eluting in a position corresponding to ~600kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ~75kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n=105) was distributed log-normally with a median value of 11μg/ml (range 4-30μg/ml). Serum and citrate plasma levels were similar, while the values in ethylenediamine tetraacetic acid plasma were slightly lower and in heparin plasma were 1·5 times higher than in serum. MASP-1 was present at adult level at 1 year of age, while it was 60% at birth. In normal healthy individuals the level of MASP-1 was stable throughout a 2-month period. After induction of an acute-phase reaction by operation we found an initial short decrease, concomitant with an increase in C-reactive protein levels, followed by an increase, doubling the MASP-1 concentration after 2 days. The present data prepare the ground for studies on the associations of MASP-1 levels with disease.

Original languageEnglish
Pages (from-to)38-48
Number of pages11
JournalClinical and Experimental Immunology
Volume169
Issue number1
DOIs
Publication statusPublished - Jul 2012

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Mannose-Binding Protein-Associated Serine Proteases
Serine Proteases
Lectins
Serum
Mannose-Binding Lectin
ethylenediamine
Buffers
Acute-Phase Reaction
Complement Activation

Keywords

  • Complement
  • Inflammation
  • Innate immunity
  • Lectin pathway

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Mannan-binding lectin (MBL)-associated serine protease-1 (MASP-1), a serine protease associated with humoral pattern-recognition molecules: Normal and acute-phase levels in serum and stoichiometry of lectin pathway components",
abstract = "The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood in complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of the MASPs occurs leading to activation of the complement system, an important component of the innate immune system. Three proteins are produced from the MASP1 gene: MASP-1 and MASP-3 and MAp44. We present an assay specific for MASP-1, which is based on inhibition of the binding of anti-MASP-1-specific antibody to MASP-1 domains coated onto microtitre wells. MASP-1 was found in serum in large complexes eluting in a position corresponding to ~600kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ~75kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n=105) was distributed log-normally with a median value of 11μg/ml (range 4-30μg/ml). Serum and citrate plasma levels were similar, while the values in ethylenediamine tetraacetic acid plasma were slightly lower and in heparin plasma were 1·5 times higher than in serum. MASP-1 was present at adult level at 1 year of age, while it was 60{\%} at birth. In normal healthy individuals the level of MASP-1 was stable throughout a 2-month period. After induction of an acute-phase reaction by operation we found an initial short decrease, concomitant with an increase in C-reactive protein levels, followed by an increase, doubling the MASP-1 concentration after 2 days. The present data prepare the ground for studies on the associations of MASP-1 levels with disease.",
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T2 - Normal and acute-phase levels in serum and stoichiometry of lectin pathway components

AU - Thiel, S.

AU - Jensen, L.

AU - Degn, S. E.

AU - Nielsen, H. J.

AU - Gál, P.

AU - Dobó, J.

AU - Jensenius, J. C.

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N2 - The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood in complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of the MASPs occurs leading to activation of the complement system, an important component of the innate immune system. Three proteins are produced from the MASP1 gene: MASP-1 and MASP-3 and MAp44. We present an assay specific for MASP-1, which is based on inhibition of the binding of anti-MASP-1-specific antibody to MASP-1 domains coated onto microtitre wells. MASP-1 was found in serum in large complexes eluting in a position corresponding to ~600kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ~75kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n=105) was distributed log-normally with a median value of 11μg/ml (range 4-30μg/ml). Serum and citrate plasma levels were similar, while the values in ethylenediamine tetraacetic acid plasma were slightly lower and in heparin plasma were 1·5 times higher than in serum. MASP-1 was present at adult level at 1 year of age, while it was 60% at birth. In normal healthy individuals the level of MASP-1 was stable throughout a 2-month period. After induction of an acute-phase reaction by operation we found an initial short decrease, concomitant with an increase in C-reactive protein levels, followed by an increase, doubling the MASP-1 concentration after 2 days. The present data prepare the ground for studies on the associations of MASP-1 levels with disease.

AB - The pattern-recognition molecules mannan-binding lectin (MBL) and the three ficolins circulate in blood in complexes with MBL-associated serine proteases (MASPs). When MBL or ficolin recognizes a microorganism, activation of the MASPs occurs leading to activation of the complement system, an important component of the innate immune system. Three proteins are produced from the MASP1 gene: MASP-1 and MASP-3 and MAp44. We present an assay specific for MASP-1, which is based on inhibition of the binding of anti-MASP-1-specific antibody to MASP-1 domains coated onto microtitre wells. MASP-1 was found in serum in large complexes eluting in a position corresponding to ~600kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ~75kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n=105) was distributed log-normally with a median value of 11μg/ml (range 4-30μg/ml). Serum and citrate plasma levels were similar, while the values in ethylenediamine tetraacetic acid plasma were slightly lower and in heparin plasma were 1·5 times higher than in serum. MASP-1 was present at adult level at 1 year of age, while it was 60% at birth. In normal healthy individuals the level of MASP-1 was stable throughout a 2-month period. After induction of an acute-phase reaction by operation we found an initial short decrease, concomitant with an increase in C-reactive protein levels, followed by an increase, doubling the MASP-1 concentration after 2 days. The present data prepare the ground for studies on the associations of MASP-1 levels with disease.

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