Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses.
Abstract: Histidine-rich glycoprotein (HRG) is an abundant plasma protein that has been identified in most mammals. We first identified whole genome sequence of equine HRG (eHRG) and succeeded to purify eHRG from plasma of horses. Since HRG interacts with various ligands, this protein is thought to be involved in immune response, coagulation, and angiogenesis. Systemic inflammatory response syndrome (SIRS) is characterized as a non-specific, clinical, pro-inflammatory immune response that damage organs and tissues in the host. Recent reports revealed that blood HRG levels in human patients with SIRS are approximately 50% lower than those in healthy controls, indicating the use of HRG as a biomarker or treatment for SIRS. SIRS is also a serious issue in equine medicine. In this study, we investigated various effects of eHRG on neutrophil functions, including adhesion, migration, phagocytosis, reactive oxygen species (ROS) production, and lysosome maturation using neutrophils isolated from horses. Microscopic observation showed that the addition of eHRG to the culture diminished adhesion of neutrophils stimulated with LPS. Using the Boyden chamber technique, we showed that eHRG reduced neutrophil chemotaxis induced by recombinant human IL-8. Luminol-dependent chemiluminescence assay demonstrated that eHRG restrained the peak of LPS-promoted ROS production from neutrophils. In contrast, eHRG promoted phagocytic activity evaluated with uptake of fluorescent dye conjugated particles, as well as lysosomal maturation assessed using fluorescent staining for lysosomes of equine neutrophils. These results indicated that eHRG acts as a dual regulator of neutrophils in horses.
Copyright © 2021. Published by Elsevier Inc.
Publication Date: 2021-04-16 PubMed ID: 34119191DOI: 10.1016/j.jevs.2021.103620Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research explores the influence of the Histidine-rich glycoprotein (HRG), a common plasma protein found in most mammals, on the function of neutrophils in horses, presumably in the context of systemic inflammatory response syndrome (SIRS). It suggests that eHRG, a particular form of HRG from horse plasma, acts as a dual regulator of neutrophil activity, by inhibiting certain functions while promoting others.
Research Paper Explanation
- The paper begins by describing Histidine-rich glycoprotein (HRG), a protein that exists abundantly in plasma across most mammalian species. For this study, the researchers particularly focused on HRG derived from horse plasma, referred to as eHRG, which they were able to isolate and purify.
- HRG interacts with a variety of ligands and is surmised to be implicated in several biological processes, including the immune response, coagulation process, and angiogenesis.
- The paper then focuses on systemic inflammatory response syndrome (SIRS), a non-specific and harmful pro-inflammatory immune response identified in clinical scenarios. It causes damage to organs and tissues in the host body. The study shows that in human SIRS patients, HRG blood levels are usually around 50% lower than in healthy subjects, which potentially indicates HRG as a potential biomarker for diagnosing SIRS or even as a form of treatment.
- The same SIRS issue exists in horse medicine as well, which is the primary basis of the conducted research.
- The scientists then evaluated various functions of neutrophils i.e., cell particles that form part of the immune system, including adhesion, migration, phagocytosis, reactive oxygen species (ROS) production, and lysosome maturation, in the presence of eHRG.
- They observed under a microscope that the addition of eHRG seemed to reduce the adhesion of neutrophils that had been stimulated with Lipopolysaccharides (LPS). Using the Boyden chamber technique, it was observed that eHRG diminished chemotaxis or movement of neutrophils as well.
- Meanwhile, the study demonstrated that eHRG, when introduced, curbed the peak of LPS-boosted ROS production grom neutrophils. ROS are chemicals that may cause damage to cells and tissues.
- On the other hand, eHRG seemingly enhanced the phagocytic activity, which relates to the uptake of pathogenic particles by immune cells, as well as the maturation of lysosomes, crucial for waste disposal in cells, as indicated by fluorescent staining.
- Putting all the findings together, the research concluded that eHRG functions as a dual regulator in horse neutrophils, impeding certain cell reactions, while enhancing others.
Cite This Article
APA
Muko R, Matsuda H, Oikawa MA, Shin T, Matsuda K, Sato H, Sunouchi T, Tanaka A.
(2021).
Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses.
J Equine Vet Sci, 102, 103620.
https://doi.org/10.1016/j.jevs.2021.103620 Publication
Researcher Affiliations
- Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Division of Animal Life Science, Institute of Agriculture, Tokyo, Japan.
- Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
- Diagnostic and Research Laboratory, Equine Veterinary Medical Center, Education City, Doha, Qatar.
- Department of Veterinary Anatomy, College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University, Jeju, South Korea.
- Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
- Ritto Training Center, Japan Racing Association, Shiga, Japan.
- Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
- Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Division of Animal Life Science, Institute of Agriculture, Tokyo, Japan; Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan. Electronic address: akane@cc.tuat.ac.jp.
MeSH Terms
- Animals
- Chemotaxis, Leukocyte
- Horse Diseases
- Horses
- Humans
- Neutrophils
- Proteins
- Systemic Inflammatory Response Syndrome / veterinary
Citations
This article has been cited 2 times.- Muko R, Sunouchi T, Urayama S, Toishi Y, Kusano K, Sato H, Muranaka M, Shin T, Oikawa MA, Ojima Y, Ali M, Nomura Y, Matsuda H, Tanaka A. Unique insertion/deletion polymorphisms within histidine-rich region of histidine-rich glycoprotein in Thoroughbred horses.. Sci Rep 2023 Jan 6;13(1):300.
- Kaneshiro N, Komai M, Imaoka R, Ikeda A, Kamikubo Y, Saito T, Saido TC, Tomita T, Hashimoto T, Iwatsubo T, Sakurai T, Uehara T, Takasugi N. Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease.. iScience 2022 Mar 18;25(3):103869.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists