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PMID:8608232

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Citation

Taub, DD, Longo, DL and Murphy, WJ (1996) Human interferon-inducible protein-10 induces mononuclear cell infiltration in mice and promotes the migration of human T lymphocytes into the peripheral tissues and human peripheral blood lymphocytes-SCID mice. Blood 87:1423-31

Abstract

The human cytokine, interferon-inducible protein-10 (IP-10), is a small glycoprotein secreted by activated monocytes, T cells, keratinocytes, astrocytes, and endothelial cells and is structurally related to the alpha subfamily of chemotactic cytokines called chemokines (Taub and Oppenheim, Cytokine 5:175, 1993). However, in contrast to other alpha chemokines that induce neutrophil migration, IP-10 has been shown to chemoattract monocytes and T lymphocytes in vitro, suggesting a role in T-cell-mediated immune responses. We therefore examined the effects of human IP-10 after in vivo administration. IP-10 induces significant mononuclear cell infiltration after subcutaneous injections in normal mice. In an effort to study the in vivo effects of IP-10 on human leukocyte migration, we then examined the ability of recombinant human IP-10 (rhIP-10) to induce human-T-cell infiltration using a human/severe combined immune deficiency (SCID) mouse model. SCID mice received an intraperitoneal injection of human peripheral blood lymphocytes (10(8) cells), followed by a subcutaneous injection of rhIP-10 (1 micrograms/injection) in the hind flank for 4 hours or sequential injections for 3 days. The skin and underlying tissue from the rhIP-10 injection site were then biopsied and examined for the extent of mononuclear cell infiltration. rhIP-10 again induced significant mononuclear cell accumulation 72 hours after injection. Immunohistologic evaluation determined that a significant number of human CD3+ T cells were recruited in response to rhIP-10 injections. These results show that rhIP-10 is capable of inducing human T-cell migration in vivo and may play an important role in monocyte and lymphocyte recruitment into inflammatory sites.

Links

PubMed

Keywords

Animals; Chemokine CXCL10; Chemokines/pharmacology; Chemokines, CXC; Chemotaxis, Leukocyte/drug effects; Cytokines/pharmacology; Humans; Mice; Mice, Inbred BALB C; Mice, SCID; Monocytes/immunology; Neutrophils/immunology; Recombinant Proteins; T-Lymphocytes/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CXL10

GO:0010819: regulation of T cell chemotaxis

ECO:0000314:

P

Figure 1A shows that addition of the chemokine rhIP-10 regulates the movement of the T-cells in vitro.

complete
CACAO 5482

HUMAN:CXL10

involved_in

GO:0090026: positive regulation of monocyte chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXL10

involved_in

GO:0010819: regulation of T cell chemotaxis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CXL10

GO:0090026: positive regulation of monocyte chemotaxis

ECO:0000314:

P

Figure 1B shows that the addition of the chemokine rhIP-10 leads to increased monocyte chemotaxis.

complete
CACAO 5483


See also

References

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