Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells.
The human cytokine interferon-inducible protein 10 (IP-10) is a small glycoprotein secreted by activated T cells, monocytes, endothelial cells, and keratinocytes, and is structurally related to a family of chemotactic cytokines called chemokines. Although this protein is present in sites of delayed-type hypersensitivity reactions and lepromatous leprosy lesions, the biological activity of IP-10 remains unknown. We report here that recombinant human IP-10 stimulated significant in vitro chemotaxis of human peripheral blood monocytes but not neutrophils. Recombinant human IP-10 also stimulated chemotaxis of stimulated, but not unstimulated, human peripheral blood T lymphocytes. Phenotypic analysis of the stimulated T cell population responsive to IP-10 demonstrated that stimulated CD4+ and CD29+ T cells migrated in response to IP-10. This resembles the biological activity of the previously described T cell chemoattractant RANTES. Using an endothelial cell adhesion assay, we demonstrated that stimulated T cells pretreated with optimal doses of IP-10 exhibited a greatly enhanced ability to bind to an interleukin 1-treated endothelial cell monolayer. These results demonstrate that the IP-10 gene encodes for an inflammatory mediator that specifically stimulates the directional migration of T cells and monocytes as well as potentiates T cell adhesion to endothelium.
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
D D
DD
Taub
A R
AR
Lloyd
K
K
Conlon
J M
JM
Wang
J R
JR
Ortaldo
A
A
Harada
K
K
Matsushima
D J
DJ
Kelvin
J J
JJ
Oppenheim
D015703:Antigens, CD / Q000032:analysis; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D015703:Antigens, CD; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D011994:Recombinant Proteins