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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5694-5703. Prepublished online as a Blood First Edition Paper on March 3, 2008; DOI 10.1182/blood-2007-12-126748. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-12-126748v1 111/12/5694    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Munitz, A. Articles by Rothenberg, M. E Search for Related Content PubMed PubMed Citation Articles by Munitz, A. Articles by Rothenberg, M. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 3, 2007 Accepted March 1, 2008 A dual activation and inhibition role for the paired immunoglobulin-like receptor B (PIR-B) in eosinophils Ariel Munitz, Melissa L McBride, Joshua S Bernstein, and Marc E Rothenberg* Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States * Corresponding author; email: rothenberg{at}cchmc.org. The accumulation of eosinophils in inflammatory foci is a hallmark characteristic of Th2 inflammation. Nevertheless, the expression of inhibitory receptors such as paired immunoglobulin-like receptor B (PIR-B) and their function regulating eosinophil accumulation has received limited attention. We now report that Pirb was upregulated in an eosinophil-dependent manner in the lungs of allergen-challenged and IL-13-overexpressing mice. Eosinophils expressed high levels of PIR-B and Pirb-/- mice displayed increased gastrointestinal eosinophils. Consistent with these findings, PIR-B negatively regulated eotaxin-dependent eosinophil chemotaxis in vivo and in vitro. Surprisingly, Pirb-/- eosinophils and neutrophils had decreased LTB4-dependent chemotactic responses in vitro. Furthermore, eosinophil accumulation was decreased in a chitin-induced model, partially dependent on LTB4. Mechanistic analysis employing a miniphosphoproteomic approach revealed that PIR-B recruits activating kinases following LTB4 but not eotaxin stimulation. Consequently, eotaxin-activated Pirb-/- eosinophils displayed markedly increased ERK1/2 phosphorylation whereas LTB4-activated eosinophils had reduced ERK1/2 phosphorylation. We provide multiple lines of evidence supporting a model in which PIR-B displays opposing but potent regulatory functions in granulocyte activation. These data change the conventional wisdom that inhibitory receptors are restricted to inhibitory signals; we therefore propose that a single receptor can have dual functionality in distinct cell types following unique cellular signals. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Eosinophils unleashed Helene F. Rosenberg Blood 2008 111: 5423. [Full Text] [PDF] This article has been cited by other articles: I. Torii, S. Oka, M. Hotomi, W. H. Benjamin Jr, T. Takai, J. F. Kearney, D. E. Briles, and H. Kubagawa PIR-B-Deficient Mice Are Susceptible to Salmonella Infection J. Immunol., September 15, 2008; 181(6): 4229 - 4239. [Abstract] [Full Text] [PDF]

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