Coreceptor chemokine receptor expression on human hematopoietic cells: Biological implications for human immunodeficiency virus-type 1 infection

被引:83
作者
Lee, B
Ratajczak, J
Doms, RW
Gewirtz, AM
Ratajczak, MZ
机构
[1] Hosp Univ Penn, Dept Med, Stellar Chance Labs 1007, Philadelphia, PA 19104 USA
[2] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
关键词
D O I
10.1182/blood.V93.4.1145.404k17_1145_1156
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The recent discovery of chemokine receptors as coreceptors for human immunodeficiency virus-type 1 (HIV-1) entry offers new avenues for investigating the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related cytopenias. To this end, we sought to (1) phenotype human hematopoietic cells for CD4 and the HIV-1 coreceptors CXCR4, CCR5, CCR3, and CCR2b; (2) correlate CD4 and chemokine receptor expression with their susceptibility to HIV-1 infection; and (3) examine any potential interplay between inflammatory cytokines released during HIV-1 infection and regulation of chemokine receptor expression. Fluorescence-activated cell sorting (FACS) analysis of bone marrow mononuclear cells (BMMNC), cells derived from serum-free expanded hematopoietic lineages (colony-forming unit-granulocyte-macrophage [CFU-GM], colony-forming unit-megakaryocyte [CFU-Meg], and burst-forming unit-erythroid [BFU-E]), and CD34(+) cells showed differential expression of chemokine receptors and GD4 with some lineage specificity. Significantly, FAGS-sorted CXCR4(+)/CD34(+) cells had the same clonogeneic potential as CXCR4(-)/CD34(+) cells. Reverse transcriptase-polymerase chain reaction (RT-PGR) analysis of FACS-sorted human candidate stem cells (HSC; CD34(+), c-kit(+) Rho123(low)) showed the presence of CXCR4 mRNA but not GD4 mRNA. Infection studies with HIV-1 Env-pseudotyped luciferase reporter viruses indicated that X4 Env (CXCR4-using) pseudotypes infected megakaryocytic cells, whereas R5 Env (CCR5-using) pseudotypes did not. Similarly, R5 but not X4 Env-pseudotyped viruses infected granulocyte-macrophage cells in a CD4/CCR5-dependent manner. Erythroid cells were resistant to R5 or X4 viral infection. Finally, we found that gamma-interferon treatment upregulated CXCR4 expression on primary hematopoietic cells. In summary, the delineation of chemokine receptor expression on primary hematopoietic cells is a first step towards dissecting the chemokine-chemokine receptor axes that may play a role in hematopoietic cell proliferation and homing. Furthermore, susceptibility of hematopoietic cells to HIV-1 infection is likely to be more complicated than the mere physical presence of CD4 and the cognate chemokine receptor. Lastly, our results suggest a potential interplay between gamma-interferon secretion and CXCR4 expression. (C) 1999 by The American Society of Hematology.
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页码:1145 / 1156
页数:12
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