CL-L1 and CL-K1 Exhibit Widespread Tissue Distribution With High and Co-Localized Expression in Secretory Epithelia and Mucosa

Abstract

Collectin liver 1 (CL-L1, alias collectin 10) and collectin kidney 1 (CL-K1, alias collectin 11) are oligomeric pattern recognition molecules associated with the complement system, and mutations in either of their genes may lead to deficiency and developmental defects. The two collectins are reportedly localized and synthesized in the liver, kidneys, and adrenals, and can be found in the circulation as heteromeric complexes (CL-LK), which upon binding to microbial high mannose-like glycoconjugates activates the complement system via the lectin activation pathway. The tissue distribution of homo- vs. heteromeric CL-L1 and -K1 complexes, the mechanism of heteromeric complex formation and in which tissues this occurs, is hitherto incompletely described. We have by immunohistochemistry using monoclonal antibodies addressed the precise cellular localization of the two collectins in the main human tissues. We find that the two collectins have widespread and almost identical tissue distribution with a high expression in epithelial cells in endo-/exocrine secretory tissues and mucosa. There is also accordance between localization of mRNA transcripts and detection of proteins, showing that local synthesis likely is responsible for peripheral localization and eventual formation of the CL-LK complexes. The functional implications of the high expression in endo-/exocrine secretory tissue and mucosa is unknown but might be associated with the activity of MASP-3, which has a similar pattern of expression and is known to potentiate the activity of the alternative complement activation pathway.

l‐Fucose prevention of renal ischaemia/reperfusion injury in Mice

“…7,8 The classical and lectin pathways begin with pattern recognition molecules (PRMs) that recognize altered cell surface or foreign ligands. 13,14 CL-11 is expressed in a number of organs 15 and within the kidney it is predominantly expressed in the renal tubules but is also present in the glomerular mesangium and epithelium. The emphasis of our study is on Collectin-11 (CL-11), a lectin pathway PRM known to have significant expression throughout major organs, 11,12 and a major focus of recent work in our lab.…”

Development of a Quantitative Assay for the Characterization of Human Collectin-11 (CL-11, CL-K1)

“…Similar low pH, low calcium conditions result from infection-induced local inflammation ( 42 ). Immunohistochemical analyses have revealed that CL-11 is expressed (among others) in the stomach and the intestines ( 11 ). At this stage we can only conjecture whether the calcium-independent zymosan interaction may be of biological relevance in acidic environments with low calcium availability.…”

“…CL-11 deficiency is one of the causes of the 3MC (Malpuech, Michels, Mingarelli, and Carnevale) syndrome ( 3 , 10 ), a congenital disorder associated with craniofacial dysmorphism, mental retardation, growth deficiency, and physical abnormalities. CL-11 is expressed ubiquitously in the body and it appears to play an important role in maintaining homeostasis in the tissue of expression ( 1 , 11 ). During embryonic development, CL-11 is highly expressed in the craniofacial cartilage and vertebral bodies, where together with MASP-3 and CL-10, may act as a guidance cue for neural crest cell migration ( 12 ).…”

Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome

“…A total of three polypeptide chains of (two of CL-K1 and one of CL-L1) join to form a heteromeric subunit, which may further oligomerize into structures ranging from dimer to hexamer (acc. to Hansen et al, 2018[41]).…”