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Chemotaxis by a CNS macrophage, the microglia
J Yao1, L Harvath, D L Gilbert
1Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, D.C. 20007.
Abstract:
Microglia demonstrate many characteristics similar to those seen in monocytes and tissue-specific macrophages, including phagocytosis, production of oxygen radicals, and growth factors and expression of MHC antigens. We have examined the ability of microglia, cultured from the cerebral cortices of neonatal rats, to demonstrate another important functional characteristic of monocytic-derived cells, that is, chemotaxis. Our results show that cultured rat microglia demonstrate chemotaxis to complement dependent chemoattractants such as recombinant C5a, zymosan activated serum, and to rat serum as well as to transforming growth factor-beta, a chemoattractant produced by platelets. Microglia fail to migrate to bacterial dependent chemoattractants such as the N-formyl peptides. The failure to respond is not dependent on maturational state of the microglia. Treatment with DMSO or casein, agents known to induce morphological and functional changes in cultured microglia reminescent of a "resting" and an "activated" macrophage, respectively, do not alter the response to fMet-Leu-Phe. In addition, the chemotactic response to serum in DMSO or casein-treated cells is the same as the response seen in untreated day 10 cultured microglia or untreated age-matched controls. The ability of microglia to migrate in response to inflammatory mediators suggests that these cells can move to sites of injury, thereby enabling them to participate in an inflammatory response.
Insights
Cultured microglia exhibit chemotaxis towards inflammatory signals like complement C5a and TGF-beta, but not bacterial peptides. This indicates microglia can migrate to injury sites, aiding inflammatory responses.
Area of Science:
- Neuroimmunology
- Cellular Biology
Background:
- Microglia share characteristics with monocytes and macrophages, including phagocytosis and antigen expression.
- Their functional repertoire, particularly chemotaxis, is crucial for immune responses in the central nervous system.
Purpose of the Study:
- To investigate the chemotactic abilities of cultured rat microglia.
- To determine if microglia migrate towards specific chemoattractants relevant to inflammation and injury.
Main Methods:
- Culturing microglia from neonatal rat cerebral cortices.
- Assessing microglial migration in response to various chemoattractants, including recombinant C5a, zymosan-activated serum, rat serum, transforming growth factor-beta, and N-formyl peptides.
- Evaluating the effect of maturational state and activation agents (DMSO, casein) on chemotaxis.
Main Results:
- Cultured microglia demonstrated chemotaxis towards complement-dependent chemoattractants (C5a, activated serum, rat serum) and transforming growth factor-beta.
- Microglia failed to migrate towards bacterial-dependent chemoattractants like N-formyl peptides.
- This migratory response was independent of microglial maturational state or activation status induced by DMSO or casein.
Conclusions:
- Cultured rat microglia possess chemotactic capabilities, responding to specific inflammatory mediators.
- Their inability to migrate towards bacterial peptides suggests a specialized role in the CNS immune response.
- Microglial migration to inflammatory sites highlights their potential to participate actively in injury and inflammatory processes within the brain.