Localization of hyaluronan and the hyaluronan receptor ICAM-1 in rheumatoid synovia—a histochemical study

Abstract

The major site for elimination of HA from the bloodstream is via receptor mediated endocytosis by liver endothelial cells (LEC) (Fraser and Laurent 1989, Laurent and Fraser 1992). The HA receptor (HAR) on LEC has been characterized and isolated from rat LEC membranes (Forsberg and Gustafson 1991). A monospecific polyclonal antibody against the 90–100 kD receptor, which could inhibit binding of HA to LEC and LEC membranes, (termed anti-HARLEC) was raised (Forsberg and Gustafson 1991). In immunohistochemical studies the antibody stains mainly endothelium such as the sinusoids in the liver, spleen and lymph nodes, some capillaries in kidney and corneal endothelial cells (Gustafson et al. 1994, Forsberg et al. 1994). Tryptic peptides of the receptor were sequenced and found to be identical to intercellular adhesion molecule-1 (ICAM-1) (McCourt et al. 1994). ICAM-1 is normally expressed at low levels, but has been found on normal liver endothelium at the sinusoids and on the endothelium of lymph nodes, spleen and some capillaries of the kidney (Dustin et al. 1986), as well as on corneal endothelial cells (Foets et al. 1992). The localization corresponds well with anti-HARLEC staining (Gustafson et al. 1994, Forsberg et al. 1994) and to tissues where HA binding and uptake have been found (Fraser and Laurent 1989, Laurent and Fraser 1992, Forsberg et al. 1994). ICAM-1 is upregulated in inflammation and neoplasia and is a key molecule for leukocyte adherence and transendothelial migration (Dustin et al. 1986, Tamatani and Miyasaka 1990, Springer 1994). We have recently also shown that HARLEC/ICAM-1, expressed on tumor endothelium in mouse mastocytomas, can bind intravenously administered radiolabeled HA (Gustafson et al. 1995).