OVERRIDING THE BRAIN'S INTRINSIC RESISTANCE TO LEUKOCYTE RECRUITMENT WITH INTRAPARENCHYMAL INJECTIONS OF RECOMBINANT CHEMOKINES
| Autor: | V.H. Perry, Dennis D. Taub, M. D. Bell |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Chemokine
Pathology medicine.medical_specialty Lipopolysaccharide Central nervous system Inflammation Blood–brain barrier Hippocampus Mice chemistry.chemical_compound Dermis Parenchyma Leukocytes medicine Animals Chemokine CCL2 Injections Spinal Recombination Genetic Mice Inbred BALB C biology business.industry General Neuroscience Monocyte Brain Immunohistochemistry medicine.anatomical_structure chemistry Immunology biology.protein Chemokines medicine.symptom business |
| Zdroj: | Neuroscience. 74:283-292 |
| ISSN: | 0306-4522 |
| DOI: | 10.1016/0306-4522(96)00083-8 |
| Popis: | Following the intracranial injection of lipopolysaccharide or during acute neuronal degeneration, there is a paucity of polymorphonuclear leukocyte recruitment to the brain parenchyma and a delay in monocyte recruitment. The present study investigates whether the injection of specific leukocyte chemoattractants into the murine central nervous system can override this intrinsic resistance. Recombinant alpha-(IL-8/NAP-1 MIP-2, IP-10) and beta-chemokines (MCP-1, RANTES) were injected into the murine hippocampus and leukocyte recruitment was assessed histologically. Injections were also made into the dermis of the hind flank for comparison. At doses of 1 microgram, MCP-1 was found to be the most potent monocyte chemoattractant in the brain parenchyma and skin with IP-10 and RANTES producing minimal monocyte recruitment to both sites. In contrast IL-8, and MIP-2 provoked dramatic polymorphonuclear leukocyte recruitment in both the central nervous system and skin. The polymorphonuclear leukocyte recruitment was associated with a breaching of the blood brain barrier that was particularly severe after MIP-2. Both L-8 and MIP-2 induced blood brain barrier breakdown could be attenuated by prior depletion of the circulating leukocytes. The regulation of polymorphonuclear leukocyte chemoattractants in the brain parenchyma during injury and infection is an important area for future studies. |
| Databáze: | OpenAIRE |
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