Recombinant human growth-regulated oncogene-alpha induces T lymphocyte chemotaxis. A process regulated via IL-8 receptors by IFN-gamma, TNF-alpha, IL-4, IL-10, and IL-13.
The human cytokine growth-regulated oncogene (GRO)-alpha is a small glycoprotein secreted by monocytes, endothelial cells, glycoprotein secreted by monocytes, endothelial cells, fibroblasts, synovial cells, and some tumor cells such as melanoma cells. It is structurally related to IL-8 and can activate neutrophils, whereas it induces chemotaxis, exocytosis, and a respiratory burst in neutrophils. To date, its functions on T lymphocytes have not been well established. We report here that recombinant human (rh)GRO-alpha is a potent chemoattractant for freshly isolated T lymphocytes, but not for anti-CD3 mAb-activated T lymphocytes. It attracts CD4+ and CD8+ T lymphocyte subsets to an equal extent. The migrating T lymphocytes toward rhGRO-alpha are predominantly CD45RO+ memory CD4+ and CD8+ subsets. The chemotactic migration of T lymphocytes toward rhGRO-alpha is stimulated via the IL-8 receptors on the cells. This process can be augmented by IFN-gamma and TNF-alpha, and inhibited by IL-4, IL-10, and IL-13. In addition, we also document that on T lymphocytes there exist IL-8 receptors that can be up-regulated by IFN-gamma, TNF-alpha, and IL-2. Our results demonstrate that rhGRO-alpha gene encodes for an inflammatory mediator that stimulates the directional migration of T lymphocytes. It may thus be another important mediator in the diseases in which T lymphocytes form the major constituent of the cellular infiltration.
Jinquan
T
T
Department of Dermatology, University of Aarhus, Denmark.
Frydenberg
J
J
Mukaida
N
N
Bonde
J
J
Larsen
C G
CG
Matsushima
K
K
Thestrup-Pedersen
K
K
D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D015703:Antigens, CD; D017252:CD3 Complex; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma