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Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes
- Source :
- Journal of Clinical Investigation. 98:529-539
- Publication Year :
- 1996
- Publisher :
- American Society for Clinical Investigation, 1996.
-
Abstract
- Chemokines (pro-inflammatory chemoattractant cytokines) are expressed in pathological conditions of the central nervous system (CNS). Previous studies suggested that the CNS is relatively resistant to leukocyte diapedesis after chemokine injection, leaving their functional role unresolved. The CNS function of N51/KC, a neutrophil-selective chemokine, was addressed by expressing N51/KC under control of the myelin basic protein (MBP) promoter in transgenic (tg) mice (MBP-N51/KC mice). CNS-specific N51/KC expression produced remarkable neutrophil infiltration into perivascular, meningeal, and parenchymal sites, demonstrating that this chemokine exerts the multiple functions in vivo required to recruit leukocytes into the CNS. MBP-N5 1/KC mice represent an incisive model for the molecular dissection of neutrophil entry into the CNS. Unexpectedly, MBP-N51/KC mice developed a neurological syndrome of pronounced postural instability and rigidity at high frequency beginning at 40 days of age, well after peak chemokine expression. 68/182 mice in one tg fine were found dead before one year of age, with prominent neurological symptoms premortem in 26 (38%). Florid microglial activation and blood-brain barrier disruption without dysmyelination were the major neuropathological alterations. Late-onset neurological symptoms in MBP-N51/KC mice may indicate unanticipated consequences of CNS chemokine expression.
- Subjects :
- Male
Chemokine
Pathology
Neutrophils
Chemokine CXCL1
Restriction Mapping
Polymerase Chain Reaction
Mice
Growth Substances
Promoter Regions, Genetic
Mice, Inbred ICR
biology
Brain
General Medicine
Oligodendroglia
medicine.anatomical_structure
Mice, Inbred DBA
Cytokines
Intercellular Signaling Peptides and Proteins
Neuroglia
Female
Chemokines
Chemokines, CXC
Infiltration (medical)
Research Article
Genetically modified mouse
medicine.medical_specialty
Recombinant Fusion Proteins
Transgene
Molecular Sequence Data
Posture
Central nervous system
Mice, Transgenic
medicine
Animals
DNA Primers
Base Sequence
Chemotactic Factors
Myelin Basic Protein
Chemotaxis
medicine.disease
Introns
Myelin basic protein
Mice, Inbred C57BL
Microscopy, Electron
Astrocytes
Immunology
biology.protein
Nervous System Diseases
Subjects
Details
- ISSN :
- 00219738
- Volume :
- 98
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....ef3d878a754758b3e987031c05f72817