EXPRESSION OF CHEMOKINE RECEPTORS BY SUBSETS OF NEURONS IN THE CENTRAL-NERVOUS-SYSTEM

IL-8 is expressed by activated and neoplastic astrocytes and enhances the survival of hippocampal neurons in vitro. Since mRNA encoding chem okine receptors have been demonstrated in brain, the expression of che mokine receptors by specific cell types in anatomic regions of the cen tral nervous system (CNS) was investigated. Archival tissues from vari ous regions of the CNS were stained with specific mAbs to the Duffy Ag /receptor for chemokines, a promiscuous receptor that binds selected c hemokines; the specific receptor for IL-8 (CXCR1); and the receptor (C XCR2) shared by IL-8 and melanoma growth stimulatory activity. The Duf fy Ag/receptor for chemokines was expressed exclusively by Purkinje ce lls in the cerebellum. Chemokine binding and radioligand cross-linking confirmed the presence of a high affinity, promiscuous chemokine rece ptor in the cerebellum. Although CXCR1 was not expressed in the CNS, C XCR2 was expressed at high levels by subsets of projection neurons in diverse regions of the brain and spinal cord, including the hippocampu s, dentate nucleus, pontine nuclei, locus coeruleus, and paraventricul ar nucleus, and in the anterior horn, interomediolateral cell column, and Clarke's column of the spinal cord. Fibers that express CXCR2 incl uded those in the superior cerebellar peduncle and the substantia gela tinosa. Immunohistochemical analysis of the involved brain tissues fro m patients with Alzheimer's disease revealed expression of CXCR2 in th e neuritic portion of plaques surrounding deposits of amyloid. These d ata suggest that chemokines may play a role in reactive processes in n ormal neuronal function and neurodegenerative disorders.