ZFIN ID: ZDB-PUB-070924-4
Live imaging of chronic inflammation caused by mutation of zebrafish Hai1
Mathias, J.R., Dodd, M.E., Walters, K.B., Rhodes, J., Kanki, J.P., Look, A.T., and Huttenlocher, A.
Date: 2007
Source: Journal of Cell Science   120(19): 3372-3383 (Journal)
Registered Authors: Dodd, M. Ernest, Huttenlocher, Anna, Kanki, John, Look, A. Thomas, Mathias, Jonathan, Rhodes, Jennifer, Walters, Kevin
Keywords: Cell migration, Inflammation, Neutrophil, Psoriasis, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Anti-Inflammatory Agents, Non-Steroidal/pharmacology
  • Cell Movement/drug effects
  • Epithelium/anatomy & histology
  • Epithelium/physiology
  • Genes, Reporter
  • Humans
  • In Situ Hybridization
  • Inflammation/metabolism
  • Inflammation/pathology*
  • Mutation*
  • Neutrophils/cytology
  • Neutrophils/drug effects
  • Neutrophils/physiology
  • Nitrobenzenes/pharmacology
  • Phenotype
  • Proteinase Inhibitory Proteins, Secretory/genetics*
  • Proteinase Inhibitory Proteins, Secretory/metabolism*
  • Serine Endopeptidases/genetics
  • Serine Endopeptidases/metabolism
  • Sulfonamides/pharmacology
  • Zebrafish*/anatomy & histology
  • Zebrafish*/embryology
  • Zebrafish*/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed: 17881499 Full text @ J. Cell Sci.
The hallmark of chronic inflammation is the infiltration and persistence of leukocytes within inflamed tissue. Here, we describe the first zebrafish chronic inflammation mutant identified in an insertional mutagenesis screen for mutants that exhibit abnormal tissue distribution of neutrophils. We identified a mutant line with an insertion in the Hepatocyte growth factor activator inhibitor 1 gene (hai1; also known as Spint1) that showed accumulation of neutrophils in the fin. The mutant embryos exhibited inflammation in areas of epidermal hyperproliferation that was rescued by knock-down of the type II transmembrane serine protease Matriptase 1 (also known as St14), suggesting a novel role for Hai1-Matriptase 1 pathway in regulating inflammation. Using time-lapse microscopy of mutant embryos that express GFP from a neutrophil-specific promoter, we found that individual neutrophils in inflamed tissue displayed random motility characterized by periods of pausing alternating with periods of motility. During periods of persistent movement the cells were highly polarized, while the pausing modes were characterized by a loss of cell polarity. In contrast to responses to acute injury, neutrophils did not exhibit clear retrograde chemotaxis or resolution of inflammation in the mutant. These findings illustrate the utility of zebrafish as a new model system to study chronic inflammation and to visualize immune responses with high resolution in vivo.