Expression of stabilin-2, a novel fasciclin-like hyaluronan receptor protein, in murine sinusoidal endothelia, avascular tissues, and at solid/liquid interfaces

Abstract

Stabilin-2, the hepatic hyaluronan receptor, has recently been cloned by us. Together with stabilin-1, stabilin-2 constitutes a novel family of fasciclin-like hyaluronan receptor homologues. Here, we analyzed expression of stabilin-2 (mStab-2) in a broad array of C57BL/6 mouse organs and tissues. While northern blot analysis showed positive expression of mStab-2 mRNA confined to liver and spleen, immunohistochemistry demonstrated mStab-2 protein expression in the endothelial sinuses of liver, lymph nodes, spleen, and bone marrow, and in specialized structures of eye, heart, brain, and kidney. Expression of mStab-2 was detected in corneal and lens epithelium, in mesenchymal cells of the heart valves, in the ependymal cells lining the ventricles in the brain, and in the prismatic epithelial cells covering the renal papillae. In pathological conditions, such as tumor growth or wound healing processes, mStab-2 was not expressed in the newly formed vasculature or other tissue components. Based on these results, we suggest that mStab-2 might be involved in the clearance of hyaluronan from the lymph or the blood circulation via the network of endothelial sinuses. At the other mStab-2-positive tissues sites that are either avascular and/or demarcate a solid/liquid interface, mStab-2 may serve to maintain tissue integrity by supporting extracellular matrix turnover or it may contribute to maintaining fluidity of bodily liquids by resorption of hyaluronan.

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

“…Unlike other molecules, which are expressed ubiquitously, stabilin-2 is expressed in specific cell types, including sinusoidal endothelial cells of the spleen, lymph node, and liver, 21 as well as macrophages. It has been reported in previous studies that stabilin-2 is only barely detectable in monocytes/macrophages.…”

“…In addition, a few studies have demonstrated that stabilin-1, the closest homologue of stabilin-2, is expressed in macrophages. 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 is expressed at high levels in the sinusoidal endothelial cells of the spleen, lymph nodes, and liver. 18,21 In this study, we present evidence that stabilin-2 is also expressed in human monocyte-derived macrophages (HMDMs). These findings compelled us to speculate that stabilin-2 may participate in the recognition and engulfment of apoptotic and aged cells in macrophages.…”

Hyaluronan Anchored to Activated CD44 on Central Nervous System Vascular Endothelial Cells Promotes Lymphocyte Extravasation in Experimental Autoimmune Encephalomyelitis

“…Another candidate is the HA receptor for endocytosis. It can be expressed on the cell surface, but it predominately localizes within sinusodial endothelia and its expression by lymphocytes has not been reported (35,36). Interestingly, antibody blockage of HA binding to HA receptor for endocytosis impairs tumor cell metastasis, a process likened to active lymphocyte extravasation (37,38).…”

Expression, Processing, and Glycosaminoglycan Binding Activity of the Recombinant Human 315-kDa Hyaluronic Acid Receptor for Endocytosis (HARE)

“…Orthologues of this receptor are present in other mammals, including cow, pig, guinea pig, rat, mouse, and human (27). Human and rat HARE are primarily found in the sinusoidal endothelial cells of the lymph nodes, liver, and spleen (28 -31).…”