Back to Search Start Over

CXCL4 is a novel nickel-binding protein and augments nickel allergy

Authors :
Yukinori Tanaka
Yasuo Endo
Shunji Sugawara
Koji Muramoto
Kanan Bando
Masayuki Kinbara
K. Shishido
Toshinobu Kuroishi
Tomohisa Ogawa
Source :
Clinical & Experimental Allergy. 47:1069-1078
Publication Year :
2017
Publisher :
Wiley, 2017.

Abstract

SummaryBackground Nickel (Ni) is the most frequent metal allergen and induces a TH1-dependent type-IV allergy. Although Ni2+ is considered to bind to endogenous proteins, it currently remains unclear whether these Ni-binding proteins are involved in Ni allergy in vivo. We previously reported the adjuvant effects of lipopolysaccharide (LPS) in a Ni allergy mouse model. As LPS induces a number of inflammatory mediators, we hypothesized that Ni-binding protein(s) are also induced by LPS. Objective The objective of this study was to purify and identify Ni-binding protein(s) from serum taken from LPS-injected mice (referred as LPS serum) and examined the augmenting effects of these Ni-binding protein(s) on Ni allergy in an in vivo model. Methods BALB/cA mice were sensitized with an i.p. injection of NiCl2 and LPS. Ten days after sensitization, mice were challenged with NiCl2 by an i.d. injection into ear pinnae. Ni-binding protein(s) were purified by Ni-affinity column chromatography and gel filtration. Results Lipopolysaccharide serum, but not serum taken from saline-injected mice, augmented ear swelling induced by Ni-allergic inflammation. Ni-binding, but not non-binding fraction, purified from LPS serum augmented Ni-allergic inflammation. Mass spectrometry and Western blotting detected CXCL4 in the active fraction. A batch analysis with Ni-sepharose and a surface plasmon resonance analysis revealed direct binding between CXCL4 and Ni2+. Recombinant CXCL4 augmented Ni-allergic inflammation and exerted adjuvant effects at the sensitization phase. Conclusions These results indicate that CXCL4 is a novel Ni-binding protein that augments Ni allergy at the elicitation and sensitization phases. This is the first study to demonstrate that the Ni-binding protein augments Ni allergy in vivo.

Details

ISSN :
09547894
Volume :
47
Database :
OpenAIRE
Journal :
Clinical & Experimental Allergy
Accession number :
edsair.doi.dedup.....158f3593ae702da7b7d460683da557c8
Full Text :
https://doi.org/10.1111/cea.12926