Immune Netw.  2019 Oct;19(5):e34. 10.4110/in.2019.19.e34.

Neutrophilic Granule Protein Is a Novel Murine LPS Antagonist

• Hong J
• Qu P
• Wuest TR
• Huang H
• Huang C
• Lin PC

• KMID: 2461198
• DOI: http://doi.org/10.4110/in.2019.19.e34

Abstract

Neutrophilic granule protein (NGP) was previously reported as a granular protein of neutrophils in mouse, but the function has not been known clearly. We found the presence of the possible signal peptide in NGP and validated this protein is circulating in the bloodstream. In our findings, NGP is being modified post-translationally in Golgi apparatus and endoplasmic reticulum, which is a universal character of secretory molecules with a signal peptide. The secreted NGP protein could be detected both in vitro and in vivo. NGP has sequence similarity with an antimicrobial protein cathelicidin, and we observed the aspect of inflammation of NGP. Interestingly, NGP interacts with the complex of LPS and LPS binding protein (LBP). This interaction blocks the binding of the complex of LPS and LBP to TLR4 and the downstream inflammatory signals. Furthermore, the inhibitory function of NGP against the inflammatory effect of LPS could be observed in both in vitro and in vivo. With these findings, we report NGP is a novel secretory protein to mask LPS and inhibit its function.

Keyword

Inflammation; Inhibitors; Lipopolysaccharides; Neutrophil; Protein binding; Cytokines

MeSH Terms

Animals
Carrier Proteins
Cytokines
Endoplasmic Reticulum
Golgi Apparatus
In Vitro Techniques
Inflammation
Lipopolysaccharides
Masks
Mice
Neutrophils*
Protein Binding
Protein Sorting Signals
Carrier Proteins
Cytokines
Lipopolysaccharides
Protein Sorting Signals