Expression of CCR-5/CXCR-4 in spinal cord of patients with AIDS.
The discovery that chemokines and their receptors (in particular CXCR-4 and CCR-5) play a role in HIV infection challenges traditional views on the pathogenesis of HIV infection in man and identifies new potential targets for therapeutic intervention. Several groups as well as our pilot study have found that increased numbers of CCR-5 positive macrophage/microglia correlate with disease severity in brains of patients with AIDS. Among HIV-related disorders, vacuolar myelopathy (VM) is the most common spinal cord disorder in patients with AIDS. The purpose of this study was to investigate the possible relationship between the expression of CCR-5/CXCR-4 and spinal cord pathology in patients with AIDS. Thirty-four spinal cords (forming two groups: without and with VM) of patients with AIDS and 6 HIV-1-negative controls were investigated by routine histological examination and immunohistochemistry. Elevated expression of CXCR-4 was found in most AIDS cases with/without neuropathological disorders (8/17 and 13/16, respectively). No CCR-5 expression was detected in HIV-1-negative controls. Among 34 cases with AIDS, expression of CCR-5 was detected in 1/16 HIV-1-positive normal spinal cords and 5/18 with VM. Despite the lack of statistical significance between the two groups (P=0.1019), our results suggest that CCR-5/CXCR-4 are present in spinal cord of patients with AIDS and that CCR-5 is more frequently found in association with VM.
An
S F
SF
Department of Neuropathology, Institute of Neurology, University College London, UK. S.An@ion.ucl.ac.uk
Osuntokun
O
O
Groves
M
M
Scaravilli
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000821:virology; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D013118:Spinal Cord Diseases / Q000378:metabolism* / Q000473:pathology / Q000821:virology*
D019713:Receptors, CCR5; D019718:Receptors, CXCR4