title: Neutrophil contributions to the induction and regulation of the acute inflammatory response in teleost fish.
abstract: Neutrophils are essential to the acute inflammatory response, where they serve as the first line of defense against infiltrating pathogens. We report that, on receiving the necessary signals, teleost (Carassius auratus) neutrophils leave the hematopoietic kidney, enter into the circulation, and dominate the initial influx of cells into a site of inflammation. Unlike mammals, teleost neutrophils represent <5% of circulating leukocytes during periods of homeostasis. However, this increases to nearly 50% immediately after intraperitoneal challenge with zymosan, identifying a period of neutrophilia that precedes the peak influx of neutrophils into the challenge site at 18 h after injection). We demonstrate that neutrophils at the site of inflammation alter their phenotype throughout the acute inflammatory response, and contribute to both the induction and the resolution of inflammation. However, neutrophils isolated during the proinflammatory phase (18 h after injection) produced robust respiratory burst responses, released inflammation-associated leukotriene B(4), and induced macrophages to increase reactive oxygen species production. In contrast, neutrophils isolated at 48 h after infection (proresolving phase) displayed low levels of reactive oxygen species, released the proresolving lipid mediator lipoxin A(4), and downregulated reactive oxygen species production in macrophages before the initiation of apoptosis. Lipoxin A(4) was a significant contributor to the uptake of apoptotic cells by teleost macrophages and also played a role, at least in part, in the downregulation of macrophage reactive oxygen species production. Our results highlight the contributions of neutrophils to both the promotion and the regulation of teleost fish inflammation and provide added context for the evolution of this hematopoietic lineage.
authors: Departments of *Biological Sciences and Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Jeffrey J
authors: JJ
authors: Havixbeck
authors: Departments of *Biological Sciences and Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Aja M
authors: AM
authors: Rieger
authors: Departments of *Biological Sciences and Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Michael E
authors: ME
authors: Wong
authors: Departments of *Biological Sciences and Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors: Jordan W
authors: JW
authors: Hodgkinson
authors: Departments of *Biological Sciences and Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada dan.barreda@ualberta.ca.
authors: Daniel R
authors: DR
authors: Barreda
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D006054:Goldfish / Q000276:immunology*; D007113:Immunity, Innate; D007668:Kidney / Q000166:cytology / Q000276:immunology; D007975:Leukotriene B4 / Q000276:immunology; D044045:Lipoxins / Q000276:immunology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst; D013997:Time Factors; D015054:Zymosan / Q000633:toxicity
chemical_list: D044045:Lipoxins; D017382:Reactive Oxygen Species; C040527:lipoxin A4; D007975:Leukotriene B4; D015054:Zymosan
keywords: comparative immunology; evolution; innate immunity; resolution of inflammation