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.
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 ∼600 kDa after gel permeation chromatography in calcium-containing buffer and as monomers of ∼75 kDa in dissociating buffer. The concentration of MASP-1 in donor sera (n = 105) was distributed log-normally with a median value of 11 µg/ml (range 4-30 µg/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.
Department of Biomedicine, Aarhus University, Denmark. st@microbiology.au.dk
S
S
Thiel
L
L
Jensen
S E
SE
Degn
H J
HJ
Nielsen
P
P
Gál
J
J
Dobó
J C
JC
Jensenius
D000210:Acute-Phase Reaction / Q000097:blood* / Q000276:immunology*; D000328:Adult; D000367:Age Factors; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002097:C-Reactive Protein / Q000032:analysis; D002850:Chromatography, Gel / Q000379:methods; D015179:Colorectal Neoplasms / Q000097:blood; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007074:Immunoglobulin G / Q000302:isolation & purification; D007223:Infant; D007231:Infant, Newborn; D037102:Lectins / Q000032:analysis / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000097:blood; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D000097604:Ficolins
D002097:C-Reactive Protein; D007074:Immunoglobulin G; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D000097604:Ficolins; C084067:MASP1 protein, human