TY - JOUR

T1 - Collectin 11 (CL-11, CL-K1) is a MASP-1/3-associated plasma collectin with microbial-binding activity

AU - Hansen, Soren

AU - Selman, Lana

AU - Palaniyar, Nades

AU - Ziegler, Karel

AU - Brandt, Jette

AU - Kliem, Anette

AU - Jonasson, Maiken

AU - Skjoedt, Mikkel-Ole

AU - Nielsen, Ole

AU - Hartshorn, Kevan

AU - Jørgensen, Thomas J D

AU - Skjødt, Karsten

AU - Holmskov, Uffe

PY - 2010/11/15

Y1 - 2010/11/15

N2 - Collectins play important roles in the innate immune defense against microorganisms. Recently, a new collectin, collectin 11 (CL-11 or CL-K1), was identified via database searches. In present work, we characterize the structural and functional properties of CL-11. Under nonreducing conditions, in gel permeation chromatography recombinant CL-11 forms disulfide-linked oligomers of 100 and 200 kDa. A mAb-based ELISA estimates the concentration of CL-11 in plasma to be 2.1 μg/ml, and the presence of CL-11 in plasma was further verified by Western blotting and mass spectrometry. Mannan-binding lectin-associated serine protease 1 (MASP-1) copurified with CL-11 and the interaction in plasma with MASP-1 and/or MASP-3 was further demonstrated using ELISA. We identified the adrenal glands, the kidneys, and the liver as primary sites of expression. CL-11 lectin activity was demonstrated by ELISA and showed that CL-11 has preference for l-fucose and d-mannose. We finally show that CL-11 binds to intact bacteria, fungi, and viruses and that CL-11 decreases influenza A virus infectivity and forms complexes with DNA. On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.

AB - Collectins play important roles in the innate immune defense against microorganisms. Recently, a new collectin, collectin 11 (CL-11 or CL-K1), was identified via database searches. In present work, we characterize the structural and functional properties of CL-11. Under nonreducing conditions, in gel permeation chromatography recombinant CL-11 forms disulfide-linked oligomers of 100 and 200 kDa. A mAb-based ELISA estimates the concentration of CL-11 in plasma to be 2.1 μg/ml, and the presence of CL-11 in plasma was further verified by Western blotting and mass spectrometry. Mannan-binding lectin-associated serine protease 1 (MASP-1) copurified with CL-11 and the interaction in plasma with MASP-1 and/or MASP-3 was further demonstrated using ELISA. We identified the adrenal glands, the kidneys, and the liver as primary sites of expression. CL-11 lectin activity was demonstrated by ELISA and showed that CL-11 has preference for l-fucose and d-mannose. We finally show that CL-11 binds to intact bacteria, fungi, and viruses and that CL-11 decreases influenza A virus infectivity and forms complexes with DNA. On the basis of the significant concentration of CL-11 in circulation and CL-11's interaction with various microorganisms and MASP-1 and/or MASP-3, it is conceivable that CL-11 plays a role in activation of the complement system and in the defense against invading microorganisms.

KW - Amino Acid Sequence

KW - Animals

KW - Base Sequence

KW - Blotting, Western

KW - Chromatography, Gel

KW - Collectins

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Immunity, Innate

KW - Immunohistochemistry

KW - Mannose-Binding Protein-Associated Serine Proteases

KW - Mass Spectrometry

KW - Molecular Sequence Data

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.4049/jimmunol.1002185

DO - 10.4049/jimmunol.1002185

M3 - Journal article

C2 - 20956340

VL - 185

SP - 6096

EP - 6104

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -