Macrophage inflammatory protein-1beta induces migration and activation of human thymocytes.
The CC chemokine macrophage inflammatory protein 1beta (MIP-1beta), has been shown to be a chemoattractant preferentially activating CD4(+) CD45RA+ T lymphocytes. Further analysis of chemokine action on lymphocytic cells has shown the potent migration-promoting capacity of MIP-1beta on human thymocytes. The responding cells were the CD4(+) and CD8(+) single-positive (SP), as well as the CD4(+) CD8(+) double-positive (DP) populations, with little if any migratory activity on the double-negative (DN) population. The activation of thymocytes by MIP-1beta appeared to be a direct, receptor-mediated event as evidenced by the rapid mobilization of intracellular calcium, increase in proteins phosphorylated on tyrosine, and activation of the mitogen-activated protein kinase (MAPK) pathway. Radioligand binding analyses showed specific and displaceable binding of MIP-1beta to thymocytes with a Kd of approximately 1 nmol/L, a profile that was comparable with MIP-1beta binding to CCR-5-transfected NIH 3T3 cells. In addition, CCR-5 mRNA was detected in total thymocyte populations indicating that activation of thymocytes by MIP-1beta may occur through binding to CCR-5. Further dissection of the subpopulations showed that only the DP and CD8(+) SP populations expressed CCR-5 and expression data on these two populations was confirmed using anti-CCR-5 monoclonal antibody. These data may be suggestive of a role for MIP-1beta in human thymocyte activation, and show a potential route for HIV infectivity in the developing immune system.
Dairaghi
D J
DJ
Department of Immunology, DNAX Research Institute, Palo Alto, CA, USA.
Franz-Bacon
K
K
Callas
E
E
Cupp
J
J
Schall
T J
TJ
Tamraz
S A
SA
Boehme
S A
SA
Taylor
N
N
Bacon
K B
KB
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000187:drug effects*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D011869:Radioligand Assay; D019713:Receptors, CCR5 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*
D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D017871:Calcium-Calmodulin-Dependent Protein Kinases