Stabilin-1 and −2 constitute a novel family of fasciclin-like hyaluronan receptor homologues

Abstract

MS-1, a high-molecular-mass protein expressed by non-continuous and angiogenic endothelial cells and by alternatively activated macrophages (Mφ2), and the hepatic sinusoidal endothelial hyaluronan clearance receptor are similar with respect to tissue distribution and biochemical characteristics. In the present study we purified these proteins by immuno- and hyaluronan-affinity chromatography respectively, sequenced tryptic peptides and generated full-length cDNA sequences in both mouse and human. The novel genes, i.e. stabilin-1 and stabilin-2, code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18–20 epidermal-growth-factor domains, one X-link domain and three to six B-(X7)-B hyaluronan-binding motifs. Northern-blotting experiments revealed the presence of both stabilins in organs with predominant endothelial sinuses such as liver, spleen and lymph node: stabilin-1 mRNA was also detected in organs with predominant Mφ2 cells, such as placenta, and in interleukin-4/glucocorticoid-stimulated Mφ2 cells in vitro. A polyclonal antibody made against human recombinant stabilin-1 confirmed the expression of stabilin-1 protein in splenic sinus endothelial cells in vivo and in Mφ2 in vitro. On the basis of high similarity at the protein level and the unique domain composition, which differs from that of all other known fasciclin-like proteins and hyaluronan receptors, stabilin-1 and stabilin-2 define a novel family of fasciclin-like hyaluronan receptor homologues that might play a role in cell—cell and cell—matrix interactions in vascular function and inflammatory processes.

Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor

“…19,21 Stabilin-1 and stabilin-2 have similar domain structures and expression patterns, and also operate as scavenger receptors. 17,19,20 In this point, stabilin-1 may be also involved in the clearance of apoptotic cells in macrophages. It remains to be determined whether two proteins are functionally linked.…”

“…16 Stabilin-2 is a large multifunctional receptor, which harbors seven FAS1 domains, four EGF-like repeats, and a link domain. Stabilin-2 was initially identified as the endocytic hyaluronan receptor on rat liver sinusoidal endothelial cells 17,18 and has also been reported to function as a scavenger receptor, which effects the endocytosis of modified LDL and glycation end products. 19,20 Stabilin-2 also has been shown to bind to Gram-negative and Gram-positive bacteria, thereby suggesting the potential involvement of stabilin-2 in the immune response.…”

βig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through αvβ5 integrin

“…Periostin, a matrix protein that is highly homologous to βig-h3, is also elevated in rat arteries after vascular injury and localized to smooth muscle cells of the neointima and adventitia and promotes migration of VSMCs (Lindner et al, 2005). Fas-1 domains of βig-h3 and related proteins such as periostin, stabilin-1, and stabilin-2 have been shown to interact with integrins and modulate cell adhesion and migration (Gillan et al, 2002;Kim et al, 2002;Politz et al, 2002). These Fas-1 domain-containing proteins thus seem to play a common role in cell adhesion and migration.…”

Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury

“…We isolated monocytes from human peripheral blood and stimulated their stabilin-1 expression in vitro (24). After 2 h of MDA-LDL incubation, we were able to detect intracellular deposits of MDA-LDL completely colocalized with stabilin-1 (SI Appendix, Fig.…”