Investigations on Collectin Liver 1*

Background: The collectin CL-L1 is a pattern recognition molecule of the innate immune system. Results: Several biological parameters are established and furnish a basis for continued investigations. Conclusion: CL-L1 has specificity similar to other collectins, is present as large oligomers in blood from birth, and is associated with MASPs. Significance: A number of novel data supporting a biological role for CL-L1 are presented. Collectins are pattern recognition molecules of the innate immune system showing binding to carbohydrate structures on microorganisms in a calcium-dependent manner. Recently, three novel collectins, collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1 and CL-11), and collectin placenta 1 (CL-P1), were discovered. The roles of these three collectins remain largely unknown. Here, we present a time-resolved immunofluorometric assay for quantification of CL-L1. The concentration of CL-L1 in donor plasma (n = 210) was distributed log-normally with a median value of 3.0 μg/ml (range 1.5–5.5 μg/ml). We observed on average 30% higher concentrations of CL-L1 in plasma as compared with serum. Size analysis by gel-permeation chromatography showed CL-L1 in serum to elute as large 700–800-kDa complexes and smaller 200–300-kDa complexes. CL-L1 showed specific binding to mannose-TSK beads in a Ca2+-dependent manner. This binding could be inhibited by mannose and glucose, but not galactose, indicating that CL-L1 binds via its carbohydrate-recognition domain and has ligand specificity similar to that of mannan-binding lectin. Western blot analysis of CL-L1 showed the presence of several oligomeric forms in serum. Ontogeny studies showed CL-L1 to be present at birth at near adult levels. CL-L1 levels exhibit low variation in healthy adults over a 1-year period. During acute-phase responses, the CL-L1 levels display only minor variations. In serum, CL-L1 was found in complexes with mannan-binding lectin-associated serine proteases, suggesting a role in the lectin pathway of complement activation. The presented data establish a basis for future studies on the biological role of CL-L1.

[1]  P. Garred,et al.  Collectin-11/MASP Complex Formation Triggers Activation of the Lectin Complement Pathway - The Fifth Lectin Pathway Initiation Complex , 2012, Journal of Innate Immunity.

[2]  S. Hansen,et al.  Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1). , 2012, Immunobiology.

[3]  S. Thiel,et al.  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 , 2012, Clinical and experimental immunology.

[4]  Yasuhiko Suzuki,et al.  Biological Functions of the Novel Collectins CL-L1, CL-K1, and CL-P1 , 2012, Journal of biomedicine & biotechnology.

[5]  S. Thiel,et al.  Studies of the Pattern Recognition Molecule H-ficolin , 2012, The Journal of Biological Chemistry.

[6]  S. Thiel,et al.  MAp19, the alternative splice product of the MASP2 gene , 2011, Journal of Immunological Methods.

[7]  U. Holmskov,et al.  Collectin 11 (CL-11, CL-K1) Is a MASP-1/3–Associated Plasma Collectin with Microbial-Binding Activity , 2010, The Journal of Immunology.

[8]  S. Thiel,et al.  Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene involved in regulation of the complement system. , 2010, Journal of immunological methods.

[9]  Brendan MacLean,et al.  Bioinformatics Applications Note Gene Expression Skyline: an Open Source Document Editor for Creating and Analyzing Targeted Proteomics Experiments , 2022 .

[10]  H. Nielsen,et al.  Characteristics and Biological Variations of M-Ficolin, a Pattern Recognition Molecule, in Plasma , 2009, Journal of Innate Immunity.

[11]  S. Thiel.  Complement activating soluble pattern recognition molecules with collagen-like regions, mannan-binding lectin, ficolins and associated proteins. , 2007, Molecular immunology.

[12]  R. Wallis,et al.  Localization and Characterization of the Mannose-Binding Lectin (MBL)-Associated-Serine Protease-2 Binding Site in Rat Ficolin-A: Equivalent Binding Sites within the Collagenous Domains of MBLs and Ficolins1 , 2007, The Journal of Immunology.

[13]  S. Thiel,et al.  Identification of the Site of Human Mannan-Binding Lectin Involved in the Interaction with Its Partner Serine Proteases: The Essential Role of Lys551 , 2007, The Journal of Immunology.

[14]  W. Motomura,et al.  Identification and Characterization of a Novel Human Collectin CL‐K1 , 2006, Microbiology and immunology.

[15]  S. Thiel,et al.  Influence of major surgery on the mannan‐binding lectin pathway of innate immunity , 2006, Clinical and experimental immunology.

[16]  S. Thiel,et al.  Collections and ficolins: humoral lectins of the innate immune defense. , 2003, Annual review of immunology.

[17]  S. Thiel,et al.  Levels of mannan-binding lectin-associated serine protease-2 in healthy individuals. , 2003, Journal of immunological methods.

[18]  S. Gygi,et al.  Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  N. Copeland,et al.  Molecular Cloning of Mouse Collectin Liver 1 , 2002, Bioscience, biotechnology, and biochemistry.

[20]  T. Suzutani,et al.  The Membrane-type Collectin CL-P1 Is a Scavenger Receptor on Vascular Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[21]  S. Thiel,et al.  Proteolytic Activities of Two Types of Mannose-Binding Lectin-Associated Serine Protease , 2000, The Journal of Immunology.

[22]  S. Thiel,et al.  Purification and Characterization of Two Mannan-Binding Lectins from Mouse Serum , 2000, The Journal of Immunology.

[23]  H. Yamazaki,et al.  Molecular Cloning of a Novel Human Collectin from Liver (CL-L1)* , 1999, The Journal of Biological Chemistry.

[24]  S. Thiel,et al.  Ontogeny of human mannan‐binding protein, a lectin of the innate immune system , 1995, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[25]  A. Persson,et al.  CP4: a pneumocyte-derived collagenous surfactant-associated protein. Evidence for heterogeneity of collagenous surfactant proteins. , 1988, Biochemistry.

[26]  J. Schilling,et al.  Isolation and characterization of the human pulmonary surfactant apoprotein gene , 1985, Nature.

[27]  S. Inoue,et al.  Isolation of a novel glycoprotein from the eggs of rainbow trout: occurrence of disialosyl groups on all carbohydrate chains. , 1978, Biochemical and biophysical research communications.

[28]  T. Kawasaki,et al.  Isolation and characterization of a mannan-binding protein from rabbit liver. , 1978, Biochemical and biophysical research communications.

[29]  J. Porath,et al.  Characterization studies on a new lectin found in seeds of Vicia ervilia , 1975, FEBS letters.

[30]  J. Bordet,et al.  Les phénomènes d'absorption et la conglutinine du sérum du boeuf , 1909 .