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Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous
J D Sedgwick1, S Schwender, H Imrich
1Institute for Virology and Immunobiology, University of Würzburg, Federal Republic of Germany.
Abstract:
In addition to the major population of infiltrating leukocytes recovered from inflamed rat central nervous system (CNS), all of which expressed high levels of leukocyte common antigen CD45, many cells were coisolated that were MRC OX42+ (complement receptor 3/CD11b) but expressed low-to-moderate levels of CD45 and major histocompatibility complex (MHC) class I molecules. Most cells from normal CNS, in contrast, lay within this latter, CD45low population. From previous in situ immunohistochemical studies, the fortuitously isolated CD45low cells were probably resident (ramified) microglia. Using irradiation chimeras, we show that resident microglia respond to inflammation by upregulating CD45, CD4, and MHC class I molecules with a minority of these cells increasing their expression of MHC class II molecules. A 3- to 4-fold increase in the number of microglia isolated from inflamed CNS provided indirect evidence that the cells had proliferated. In normal CNS, a very small population of blood-derived CD45high-expressing cells are present; most MHC class II expression is associated with these few cells and not with the resident microglia.
Insights
Resident microglia in the central nervous system (CNS) activate during inflammation, upregulating CD45 and MHC molecules. This study reveals microglia proliferation and altered immune marker expression in inflamed CNS environments.
Area of Science:
- Neuroimmunology
- Cell Biology
Background:
- The central nervous system (CNS) harbors resident immune cells, primarily microglia.
- Microglia exhibit distinct phenotypes based on their activation state and origin (resident vs. blood-derived).
- Leukocyte common antigen CD45 and major histocompatibility complex (MHC) molecules are key markers for immune cell identification and activation.
Purpose of the Study:
- To investigate the phenotypic changes and proliferation of resident microglia in response to CNS inflammation.
- To differentiate between resident microglia and infiltrating leukocytes in inflamed CNS tissue.
- To characterize the expression of CD45, CD4, and MHC molecules on microglia during inflammation.
Main Methods:
- Isolation and characterization of cells from normal and inflamed rat CNS.
- Flow cytometry analysis of CD45, MRC OX42 (CD11b), and MHC class I/II expression.
- Irradiation chimera model to track cell origins and behavior.
Main Results:
- Inflamed CNS contains infiltrating leukocytes (CD45high) and activated resident microglia (CD45low-to-moderate).
- Resident microglia upregulate CD45, CD4, and MHC class I upon inflammation; a subset upregulates MHC class II.
- A 3- to 4-fold increase in microglia numbers suggests proliferation during inflammation.
Conclusions:
- Resident microglia are dynamic cells that respond to CNS inflammation by altering their immune marker profile and proliferating.
- Distinguishing between resident microglia and infiltrating immune cells is crucial for understanding neuroinflammatory processes.
- Microglia play a significant role in the immune response within the CNS.