T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo.
IL-8 has been shown to be a human neutrophil and T cell chemoattractant in vitro. In an effort to assess the in vivo effects of IL-8 on human leukocyte migration, we examined the ability of rhIL-8 to induce human T cell infiltration using a human/mouse model in which SCID mice were administered human peripheral blood lymphocytes intraperitoneally, followed by subcutaneous injections of rhIL-8. rhIL-8 induced predominantly murine neutrophil accumulation by 4 h after administration while recombinant human macrophage inflammatory protein-1beta (rhMIP-1beta) induced both murine monocytes and human T cell infiltration during the same time period as determined by immunohistology. Interestingly, 72 h after chemokine administration, a marked human T cell infiltrate was observed in the IL-8 injection site suggesting that rhIL-8 may be acting indirectly possibly through a murine neutrophil-derived T cell chemoattractant. This hypothesis was confirmed using granulocyte-depleted SCID mice. Moreover, human neutrophils stimulated in vitro with IL-8 were found to release granule-derived factor(s) that induce in vitro T cell and monocyte chemotaxis and chemokinesis. This T cell and monocyte chemotactic activity was detected in extracts of both azurophilic and specific granules. Together, these results demonstrate that neutrophils store and release, upon stimulation with IL-8 or other neutrophil activators, chemoattractants that mediate T cell and monocyte accumulation at sites of inflammation.
Taub
D D
DD
Clinical Services Program, SAIC-Frederick, Fredrick Cancer Research And Development Center-National Cancer Institute, MD 21702-1201.
Anver
M
M
Oppenheim
J J
JJ
Longo
D L
DL
Murphy
W J
WJ
D000818:Animals; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte; D003594:Cytoplasmic Granules / Q000502:physiology / Q000648:ultrastructure; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000502:physiology; D015846:Monokines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
D054407:Chemokine CCL4; D006131:Growth Inhibitors; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine