Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system.

TLDR

In inflamed rat CNS, a CD45low, MRC OX42+ population—likely resident microglia—was isolated alongside infiltrating CD45high leukocytes, whereas in normal CNS this CD45low group predominates and only a few CD45high cells express MHC class II. Irradiation chimeras revealed that resident microglia upregulate CD45, CD4, and MHC class I during inflammation, with a subset also increasing MHC class II. Microglia numbers increased 3–4-fold in inflamed CNS, indicating proliferation.

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.