The limited infectability by R5 HIV of CD34(+) cells from thymus, cord, and peripheral blood and bone marrow is explained by their ability to produce beta-chemokines.
The resistance of human bone marrow (BM) CD34(+) cells to human immunodeficiency virus (HIV) infection is at this point not fully understood. Recently we reported that the chemokines MIP-1alpha, MIP-1beta, and RANTES secreted by BM-derived CD34(+) cells may compete with the macrophagotropic HIV (R5 HIV) strain for the CCR5 coreceptor.In this study we extended our previous observations and examined various lympho-hematopoietic CD34(+) cells isolated from thymus (Th), cord blood (CB), mobilized peripheral blood (mPB), and BM for the expression of beta-chemokines binding to CCR5, i.e., MIP-1alpha, MIP-1beta, RANTES, MCP-2, MCP-3, and MCP-4, and the alpha chemokine SDF-1 (binding to CXCR4) as these chemokines may compete with the R5 and X4 HIV strains, respectively, for entry into cells. We found that Th-, CB-, mPB-, and BM-derived CD34(+) cells express mRNA transcripts for all the beta-chemokines tested but not for SDF-1. Using sensitive ELISA assays we found that although MIP-1alpha and MIP-1beta proteins were secreted by all the lympho-hematopoietic CD34(+) cells tested, RANTES was detectable only in media conditioned by BM- and CB-derived CD34(+) cells and not Th-derived cells. However, media conditioned by BM-, mPB- and Th-derived CD34(+) cells protected the T lymphocytic cell line (PB-1) from infection by the R5 but not the X4 HIV strain. Hence this study demonstrates that beta-chemokines are secreted by lympho-hematopoietic CD34(+) cells originating from various sources and that these endogenously secreted chemokines may limit entry of the R5 HIV strain into the cells by competing for the CCR5 coreceptor.
Majka
M
M
Department of Pathology & Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Rozmyslowicz
T
T
Ratajczak
J
J
Dobrowsky
A
A
Pietrzkowski
Z
Z
Gaulton
G N
GN
Janowska-Wieczorek
A
A
Ratajczak
M Z
MZ
D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics / Q000502:physiology; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D017077:Culture Media, Conditioned; D016207:Cytokines; D005312:Fetal Blood / Q000166:cytology*; D015870:Gene Expression; D006678:HIV / Q000472:pathogenicity*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000821:virology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000502:physiology; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology*
D018952:Antigens, CD34; C099677:CCL13 protein, human; C515450:CCL7 protein, human; C515453:CCL8 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054412:Chemokine CCL8; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5