Premium
Elevated complement C5a receptor expression on neurons and glia in astrocyte‐targeted interleukin‐3 transgenic mice
Author(s) -
Paradisis P. Maria,
Campbell Iain L.,
Barnum Scott R.
Publication year - 1998
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199811)24:3<338::aid-glia8>3.0.co;2-y
Subject(s) - biology , astrocyte , glial fibrillary acidic protein , in situ hybridization , complement receptor , microglia , neuroinflammation , genetically modified mouse , neuroglia , pathology , inflammation , immunology , central nervous system , neuroscience , complement system , transgene , immunohistochemistry , gene expression , antibody , medicine , gene , biochemistry
Evidence from several central nervous system (CNS) inflammatory disease models suggests that intrathecal complement synthesis may contribute to early inflammatory events in the brain. In this study, we examined the expression of the receptor for C5a (C5aR), a potent inflammatory and chemotactic factor, in the brains of transgenic mice with constitutive astrocyte expression of interleukin‐3 (IL‐3), a hematopoietic and immunomodulatory cytokine. By in situ hybridization, we demonstrated that cells infiltrating the cerebellar meninges, the cerebellum, and demyelinating lesions in the cerebellum were strongly positive for C5aR mRNA. By immunohistochemistry, the infiltrating cells expressing the C5aR were identified as macrophages based on staining with antibodies to the complement receptor type 3 and F4/80, a mouse macrophage‐specific marker. In addition, some of the cells in cerebellar lesions were positive for the astrocyte‐specific marker, glial fibrillary acidic protein, suggesting that a subpopulation of astrocytes in these lesions express elevated levels of the C5aR. Increased C5aR expression was also observed in cortical neurons in the occipital cortex and in pyramidal neurons in the cornu ammonis and subiculum of the hippocampus, at both the protein and mRNA levels. These data suggest that IL‐3 may play an immunomodulatory role in C5aR expression on several cell types in the brain and that increased C5aR expression correlates with the pathology seen in this model. The transgenic mice used in this study provide a useful tool for characterizing the mechanism of regulation of the C5aR expression and for examining the functions of this chemotactic receptor in CNS inflammation. GLIA 24:338–345, 1998. © 1998 Wiley‐Liss, Inc.