Human Vascular Endothelial Cells Express Pattern Recognition Receptors for Fungal Glucans Which Stimulates Nuclear Factor κB Activation and Interleukin 8 Production

Abstract

Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity via interaction with membrane receptors on macrophages, neutrophils, and natural killer cells. We investigated the binding of water-soluble glucans in primary cultures of normal human coronary or dermal vascular endothelial cells (VECs). Membranes from VECs exhibited saturable binding. Competition studies demonstrated the presence of at least two glucan binding sites on VECs. Glucan phosphate competed for all binding sites with a K_D of 3.7 μm for coronary VECs and 11 μm for dermal VECs, respectively. Laminarin, a low molecular weight glucan, competed for 47 to 51 per cent of binding (K_D = 2.8–2.9 μm), indicating the presence of at least two binding sites. Glucan (1 μg/mL) stimulated VEC nuclear factor κB nuclear binding activity and Interleukin 8 expression—but not that of vascular endothelial growth factor—in a time-dependent manner. This is the first report of pattern recognition receptors for glucan on human VECs. It also provides the first evidence that glucans can directly modulate the functional activity of VECs by stimulating cytokine gene. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal cell wall products and suggests that the response to glucans may not be confined to leukocytes.