Cyclophilin C-associated protein:: A normal secreted glycoprotein that down-modulates endotoxin and proinflammatory responses in vivo

Mouse cyclophilin C-associated protein (Cy-CAP) is a member of the scavenger-receptor cysteine-rich domain superfamily and is 69% identical to the human Mac-2 binding protein. Here. we show that Cy AP is a fidelity expressed secreted glycoprotein that modulates the host response to endotoxin., Gene targeted CyCAP-deficient mice are more sensitive type to the lethal effects of endotoxin, In response to endotosin, CyCAP-deficient mice overproduced intereuliin 12 and interferon-gamma systemically and tumor necrosis factor Lu locally; these are proinflammatotry molecules that also promote T helper 1 responses. Furthermore, macrophages stimulated in vitro with endotosin in serum deficient in CyCAP secreted more tumor necrosis factor alpha, supporting the proposal that CyCAP specifically dorm-modulates endotosin signaling.