Human eotaxin-induces α4 and β2 integrin-dependent eosinophil accumulation in rat skin in vivo: Delayed generation of eotaxin in response to IL-4

Maria Jesus Sanz, Paul D. Ponath, Charles R. Mackay, Walter Newman, Masayuki Miyasaka, Tayuka Tamatani, Brian F. Flanagan, Roy R. Lobb, Timothy J. Williams, Sussan Nourshargh, Peter J. Jose

Research output: Contribution to journalArticleResearchpeer-review

9 Citations (Scopus)


The CC chemokine eotaxin, originally purified from bronchoalveolar lavage fluid of sensitized guinea pigs following allergen challenge, is a potent eosinophill-selective chemoattractant. In the present study, we have used 111In-eosinophils and human eotaxin to characterize the profile of chemokine-induced eosinophil accumulation in vivo in rat skin. Intradermally injected eotaxin caused a dose-dependent accumulation of 111In- eosinophils. Time course studies indicated that the response was rapid, since all the accumulation occurred within the first 1 to 2 h of eotaxin injection. The i.v. administration of anti-intercellular adhesion molecule-1, anti- vascular, cell adhesion molecule-1, or anti-α4 integrin mAbs significantly inhibited the eosinophil accumulation induced by 100 pmol of human eotaxin by 73, 43, and 67%, respectively. Further, when 111In-eosinophils were pretreated in vitro with anti-α4 integrin or anti-β2 integrin mAbs, or with a combination of both mAbs, eotaxin-induced response in vivo were reduced by 52, 49, and 68%, respectively. Eosinophil accumulation induced by intradermal IL-4, but not that induced by TNF-α or leukotriene B4, appeared to be mediated in part by endogenously generated eotaxin. Anti-eotaxin Abs significantly inhibited (54%) the later phase (24-28 h) but not the early phase (0-4 h) of the response to IL-4. This was consistent with eotaxin mRNA expression peaking at 18 h after IL-4 injection. Our findings show that human eotaxin is a potent inducer of eosinophil accumulation in vivo, this response being dependent on α4, integrin/vascular cell adhesion molecule-1 and β2 integrin/intercellular adhesion molecule-1 adhesion pathways. Further, the eosinophil accumulation in response to IL-4 is partly mediated by endogenously generated eotaxin.

Original languageEnglish
Pages (from-to)3569-3576
Number of pages8
JournalJournal of Immunology
Issue number7
Publication statusPublished - 1 Apr 1998
Externally publishedYes

Cite this