A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex

Abstract

The NK gene complex is a region on human chromosome 12 containing several families of lectin‐like genes including the CD94 and NKG2 NK receptor genes. We report here that the region telomeric of CD94 contains in addition to the LOX‐1 gene the novel human DECTIN‐1 and the CLEC‐1 and CLEC‐2 genes within about 100 kb. Sequence similarities and chromosomal arrangement suggest that these genes form a separate subfamily of lectin‐like genes within the NK gene complex. DECTIN‐1 is selectively expressed in dendritic cells and to a lowerextent in monocytes and macrophages. mRNA forms with and without a stalk exon are observed. During functional maturation of dendritic cells the level of DECTIN‐1 mRNA is down‐regulated several‐fold. CLEC‐1 is found to be not only expressed in dendritic cells, but also in endothelial cells and in the latter aspect resembles the LOX‐1 gene. Whereas recombinant full‐length DECTIN‐1 and LOX‐1 are transported to the cell surface, CLEC‐1 proteins accumulate in perinuclear compartments. We propose that this family of lectin‐like genes encodes receptors with important immune and/or scavenger functions in monocytic, dendritic and endothelial cells.

Candida albicans Triggers Activation of Distinct Signaling Pathways to Establish a Proinflammatory Gene Expression Program in Primary Human Endothelial Cells

“…It therefore seems unlikely that TLR4 is critical for signal perception of the yeast even more because siRNA against TLR4 failed to abolish Candida-induced CXCL8/IL-8 expression in ECs. According to our expression analysis (data not shown) and in line with an earlier report (47), dectin-1, the myeloid cell-expressed major receptor for fungal ␤-glucan, is not expressed by ECs thus excluding a role in Candidainduced endothelial signaling. Furthermore, the mannose receptor, another C-type lectin receptor, is absent in HUVEC (48).…”

Human MICL (CLEC12A) is differentially glycosylated and is down‐regulated following cellular activation

“…Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells.…”

“…The study of these activationand inhibitory NK cell receptorshas generated a number of interesting hypotheses, including immune privilege [1], the recognition of 'missing self', 'non-self' and 'induced self' [2][3][4][5], as well elucidating the underlying mechanisms of some of the immune responses to viruses [6] and malignancy [7]. Others and we have demonstrated that C-type lectinlike receptors are not restricted to NK cells, but are expressed by many other cell types including myeloid cells [8][9][10]. This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells.…”

“…This introduces the novel concept that the myeloid paralogs of NK cell receptors might govern myeloid cell activation/inhibition in the same manner as those on NK cells. The genes of most C-type lectin-like molecules are located within the 'natural killer complex' (NKC), but many of those expressed by myeloid and other cells are found in a distinct cluster of genes within the NKC [10]. This cluster includes Dectin-1/ betaglucan receptor [11], the lectin-like receptor for oxidized LDL (LOX-1) [12], CLEC-1 and CLEC-2 [13], two unstudied transcripts [14], and myeloid inhibitory C-type lectin-like receptor (MICL) [14].…”

Fucoidan Is a Novel Platelet Agonist for the C-type Lectin-like Receptor 2 (CLEC-2)

“…Pharmacological activity of this compound was tested in several animal models in vitro and in vivo. In humans, in vitro experiments with fucoidan demonstrated several beneficial effects on ulcers and bleeding disorders (11,12). Non-anticoagulatory sulfated polysaccharides were originally considered as a novel approach to improve coagulation because of their inhibitory effect on physiological anticoagulation, especially fucoidan, which inhibits tissue factor pathway inhibitor and accelerates clotting in hemophilia A and B patients (8).…”