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

Dennis D. Taub, Miriam Anver, Joost J. Oppenheim, Dan L. Longo, William J Murphy

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

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-1β (rhMIP-1β) 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.

Original languageEnglish (US)
Pages (from-to)1931-1941
Number of pages11
JournalJournal of Clinical Investigation
Volume97
Issue number8
StatePublished - Apr 15 1996
Externally publishedYes

Keywords

  • chemotaxis
  • granules
  • neutrophils
  • T lymphocytes

ASJC Scopus subject areas

  • Medicine(all)

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