LYVE-1, a receptor molecule for hyaluronan, is expressed in the lymphatic endothelium, blood sinus endothelium, and certain macrophage lineages. The present immunohistochemical study revealed a broader distribution of LYVE-1 in vascular endothelial cells of the murine lung, adrenal gland, and heart as well as the liver and spleen. In addition, sinus reticular cells-including sinuslining cells-in the medulla of the lymph node also intensely expressed LYVE-1. Ultrastructurally, immuno-gold particles for LYVE-1 were localized on the entire length of plasma membrane in all cell types. Most of these LYVE-1-expressing cells had previously been classified as the reticuloendothelial system (RES) specialized for eliminating foreign particles. An LPS stimulation decreased the LYVE-1 expression in macrophages but elevated the expression at mRNA and protein levels in the liver and lung, major organs for the elimination of blood-born waste substances. LYVE-1-expressing endothelial cells in these organs participated in the endocytosis of exogenous particles, and the uptake ability was conspicuously enhanced by the LPS challenge. Although the expression of the degrading enzyme, hyaluronidase, was generally low in the LYVE-1-expressing cells, they were topographically associated with a dense distribution of macrophages possessing hyaluronidase activities in each tissue. These findings suggest that the LYVE-1-expressing cells might be involved in the uptake of hyaluronan and other waste products as well as foreign particles circulating in the blood and lymph while participating in the subsequent degradation in relay with adjacent macrophage populations. LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1) has been identified as a reliable marker that is expressed predominantly in the lymphatic endothelium (5, 29). Both the chemical structure and function of LYVE-1 resemble those of a well-established hyaluronan receptor, CD44, which has a 41% similarity to LYVE-1 and is characterized as an inflammatory leukocyte homing receptor. CD44 is widely expressed in the epithelium, mesothelium, mesenchymal cells, and cells of hematopoietic origin (22), while LYVE-1 has been shown in early studies to display a restricted distribution to the lymphatic endothelium and be completely absent from blood vessels, except for sinusoidal endothelial cells in the spleen (5). Subsequent studies have also detected the expression of LYVE-1 in sinusoidal endothelial cells using paraffin sections of the liver, spleen and lymph node of humans (1, 26). However, our preliminary immunohistochemical study using frozen sections from rodents found a broader distribution of LYVE-1 in the endothelium of other organs, including the lung, adrenal gland, heart, and adenohypophysis. In addition, the sinus reticular cells in the medulla of the lymph node intensely expressed LYVE-1. Interestingly, most of these belong