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CXCL4 is a novel nickel-binding protein and augments nickel allergy
- 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.
- Subjects :
- Lipopolysaccharides
0301 basic medicine
Nickel allergy
Allergy
Lipopolysaccharide
Immunology
Inflammation
Platelet Factor 4
medicine.disease_cause
law.invention
Mice
03 medical and health sciences
chemistry.chemical_compound
Allergen
Nickel
law
Hypersensitivity
medicine
Animals
Immunology and Allergy
Sensitization
Mice, Inbred BALB C
Chemistry
medicine.disease
Molecular biology
Blot
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Recombinant DNA
medicine.symptom
Subjects
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