RT Journal Article
SR Electronic
T1 The Novel Lipopolysaccharide-Binding Protein CRISPLD2 Is a Critical Serum Protein to Regulate Endotoxin Function
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 6646
OP 6656
DO 10.4049/jimmunol.0802348
VO 183
IS 10
A1 Wang, Zhi-Qin
A1 Xing, Wen-Ming
A1 Fan, Hua-Hua
A1 Wang, Ke-Sheng
A1 Zhang, Hai-Kuo
A1 Wang, Qin-Wan
A1 Qi, Jia
A1 Yang, Hong-Meng
A1 Yang, Jie
A1 Ren, Ya-Na
A1 Cui, Shu-Jian
A1 Zhang, Xin
A1 Liu, Feng
A1 Lin, Dao-Hong
A1 Wang, Wen-Hui
A1 Hoffmann, Michael K.
A1 Han, Ze-Guang
YR 2009
UL http://www.jimmunol.org/content/183/10/6646.abstract
AB LPS is an immunostimulatory component of Gram-negative bacteria. Acting on the immune system in a systemic fashion, LPS exposes the body to the hazard of septic shock. In this study we report that cysteine-rich secretory protein LCCL domain containing 2 (CRISPLD2/Crispld2; human and mouse/rat versions, respectively), expressed by multitissues and leukocytes, is a novel LPS-binding protein. As a serum protein, median CRISPLD2 concentrations in health volunteers and umbilical cord blood samples are 607 μg/ml and 290 μg/ml, respectively. Human peripheral blood granulocytes and mononuclear cells including monocytes, NK cells, and T cells spontaneously release CRISPLD2 (range, 0.2–0.9 μg/ml) and enhance CRISPLD2 secretion (range, 1.5–4.2 μg/ml) in response to stimulation of both LPS and humanized anti-human TLR4-IgA Ab in vitro. CRISPLD2 exhibits significant LPS binding affinity similar to that of soluble CD14, prevents LPS binding to target cells, reduces LPS-induced TNF-α and IL-6 production, and protects mice against endotoxin shock. In in vivo experiments, serum Crispld2 concentrations increased in response to a nontoxic dose of LPS and correlated negatively with LPS lethality, suggesting that CRISPLD2 serum concentrations not only are indicators of the degree of a body’s exposure to LPS but also reflect an individual’s LPS sensitivity.