EXPRESSION OF THE RECEPTOR FOR COMPLEMENT C5A (CD88) IS UP-REGULATED ON REACTIVE ASTROCYTES, MICROGLIA, AND ENDOTHELIAL-CELLS IN THE INFLAMED HUMAN CENTRAL-NERVOUS-SYSTEM

C5a receptor (C5aR, CD88) is a receptor originally described on neutro phils and monocyte-macrophages but recently found on hepatocytes, epit helial cells, endothelial cells, and tissue mast cells. We recently re ported that human fetal astrocytes expressed a functional C5aR in vitr o. Here we examine C5aR expression in adult brain cultures by immunost aining with six different anti-C5aRs and show that C5aR is expressed c onstitutively by astrocytes, microglia, and fibroblast-like cells but not by oligodendrocytes. In fetal brain cultures we confirmed that ast rocytes constitutively expressed C5aR and demonstrated that fetal micr oglia and fibroblast-like cells but not oligodendrocytes and neurons e xpressed C5aR. Incubation with inflammatory cytokines (interferon gamm a, interleukin-1, and tumor necrosis factor alpha) or phorbol ester fa iled to induce or up-regulate C5aR expression on fetal or adult brain cells. Immunohistochemistry was performed to determine the expression and distribution of C5aR in the normal and inflamed brain. In the norm al brain C5aR was minimally expressed, whereas in inflamed brains from a variety of pathologies, C5aR expression was greatly up-regulated on reactive astrocytes and microglia and to a lesser extent on endotheli al cells. We propose that expression of C5aR is a marker of central ne rvous system inflammation, and that C5aR expression on brain cells in inflammation plays an important role in cell activation and recruitmen t (gliosis).