title: Differences are evident within the CXCR4-CXCL12 axis between ethnically divergent South African populations.
abstract: The G-protein-coupled receptor, CXCR4, is highly expressed on a number of cell types, and together with its ligand, CXCL12, plays an important role in immune development and trafficking of cells. CXCR4 promotes tumor growth, angiogenesis and metastasis, and is a prognostic marker in a number of different types of tumors. Additionally, CXCR4 is utilized, together with CD4, for entry of T-tropic HIV viruses. Ethnic differences in incidence and mortality of various cancers, and in the response to highly active antiretroviral treatment (HAART) of HIV-1 infected individuals have been reported. The aim of this study was to establish if differences in the CXCR4-CXCL12 axis exist between ethnically divergent uninfected South Africans. CXCR4 density was significantly higher on CD4(+) and CD8(+) T cells, B cells and CD56(dim) NK cells, and CXCL12 levels lower in Black compared with Caucasian individuals. Furthermore, an inverse correlation was observed between CXCR4 density on CD56(+) and CD3(+) cells and age, only in Black individuals. CXCL12-3'A heterozygosity (AG) found in 28% of Caucasians did not explain the higher plasma levels of CXCL12 compared to Black individuals who were all GG genotypes, suggesting that other factors influence homeostatic levels of CXCL12. In conclusion, this study demonstrates that ethnically divergent populations show clear differences in both CXCR4 density and CXCL12 plasma levels which may influence the course of cancer and HIV-1 infection.
authors: Centre for HIV and STIs, National Institute for Communicable Diseases, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors: Sharon
authors: S
authors: Shalekoff
authors: Diana B
authors: DB
authors: Schramm
authors: Ria
authors: R
authors: Lassaunière
authors: Anabela C P
authors: AC
authors: Picton
authors: Caroline T
authors: CT
authors: Tiemessen
mesh_terms: D000328:Adult; D017677:Age Distribution; D044383:Black People; D054377:Chemokine CXCL12 / Q000097:blood / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction; D013019:South Africa; D044465:White People; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4