FEEL-1, a Novel Scavenger Receptor with in Vitro Bacteria-binding and Angiogenesis-modulating Activities

Abstract

Employing the expression cloning technique, we cloned a novel scavenger receptor that is structurally unrelated to other scavenger receptors. The cloned receptor contained fasciclin (Fas-1), epidermal growth factor (EGF)-like, laminin-type EGF-like, and link domains. Based on the domain structures, we temporarily named it FEEL-1 (fasciclin, EGF-like, laminin-type EGF-like, and link domain-containing scavenger receptor-1). A data base search suggested the presence of a paralogous gene of FEEL-1, the full-length cDNA of this gene was also cloned, and its nucleotide sequence was determined. The deduced amino acid sequence of the clone indicated that its domain organization is similar to FEEL-1, and we named this clone FEEL-2. The effect of monoclonal antibodies against FEEL-1 indicated that FEEL-1 is the major receptor for 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbo-cyanine perchlorate (DiI)-labeled acetylated low density lipoprotein (DiI-Ac-LDL) in human umbilical vein endothelial cells. Reverse transcription and PCR analysis revealed that both FEEL-1 and FEEL-2 were expressed in several tissues and expressed highly in the spleen and lymph node. On the other hand, only FEEL-1 was expressed in mononuclear cells, particularly resting CD14(+) cells. The transient expression of FEEL-1 and FEEL-2 in Chinese hamster ovary cells demonstrated that both FEELs could bind to DiI-Ac-LDL. Both receptors were also found to bind to Gram-negative and Gram-positive bacteria. These results suggest that FEELs play important roles in the defense mechanisms against bacterial infection. Finally, the phenotypic effect of the inhibition of FEEL-1 on vascular remodeling was tested in vitro using the Matrigel tube formation assay, and we found a marked reduction in the degree of cell-cell interaction in anti-FEEL-1 monoclonal antibody-treated cells, suggesting the role of this receptor in angiogenesis.