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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5423. This Article Full Text (PDF) 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rosenberg, H. F. Search for Related Content PubMed PubMed Citation Articles by Rosenberg, H. F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Comment on Munitz et al, page 5694 Eosinophils unleashed Helene F. Rosenberg NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASE (NIAID) LABORATORY OF ALLERGIC DISEASES In this issue of Blood, Munitz and colleagues demonstrate pronounced expression of the inhibitory receptor known as paired immunoglobulin-like receptor (PIR)–B on the surface of mouse eosinophils. PIRs were first identified by Hayami et al1 during a search for mouse orthologs of the Fc receptor for immunoglobulin A (IgA). PIR-A and PIR-B are not IgA receptors, but have since been characterized as orthologs of the human leukocyte immunoglobulin-like receptors (LILRs); PIR-B has 6 Ig-like domains and 4 immunoreceptor tyrosine-based inhibitory motifs (ITIMs), binds to MHC class I ligands, and typically serves to diminish cellular activation.2,3 The finding that eosinophils express PIR-B is in and of itself not particularly surprising, as PIR-B has already been detected on the surface of mast cells, macrophages, and neutrophils. Similarly unsurprising is the finding that eosinophils isolated from PIR-B gene-deleted mice are effectively "unleashed," and display augmented responses to the chemoattractant eotaxin-1 both in vitro and in vivo. However, rather more remarkable are the observations that eosinophils (and neutrophils) from the same PIR-B gene-deleted mice display diminished responses to the stimulatory ligand LTB4, and that eosinophil accumulation is reduced in response to chitin and thioglycolate, both stimuli that elicit chemotaxis at least in part based on responses to LTB4. The first question is, of course: what are the molecular mechanisms underlying this original and unexpected finding? Moreover, how does a molecule with consensus-inhibitory motifs turn around and effectively augment specific cellular inflammatory responses? Is this unusual response unique to the LTB4-BLT1 ligand-receptor pair? In other words, might the PIR-B gene deletion or PIR-B functional blockade have a unique and unexpected impact on BLT1 receptor expression and/or its signal transduction response? Furthermore, there have been no published reports addressing the expression of the paired activating receptor PIR-A in mouse eosinophils, nor is there any information available on the role of PIR-A in modulating the responses of wild-type and/or PIR-B gene-deleted eosinophils to specific inflammatory stimuli. In summary, Munitz and colleagues present an intriguing and unexpected finding, one that will certainly unleash our intellectual inhibitions as we continue to explore the role of eosinophils together with this class of immunomodulatory cell-surface receptors. Acknowledgment: Ongoing work in Dr Rosenberg's laboratory is supported by the NIAID Division of Intramural Research. Please address all correspondence to Dr Rosenberg at hrosenberg{at}niaid.nih.gov. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Hayami K, Fukuta D, Nishikawa Y, et al. Molecular cloning of a novel murine cell-surface glycoprotein homologous to killer cell inhibitory receptors. J Biol Chem. 1997;272:7320–7327.[Abstract/Free Full Text] Katz HR. Inhibitory receptors and allergy. Curr Opin Immunol. 2002;14:698–704.[CrossRef][Medline] [Order article via Infotrieve] Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology. 2005;115:433–440.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils Ariel Munitz, Melissa L. McBride, Joshua S. Bernstein, and Marc E. Rothenberg Blood 2008 111: 5694-5703. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rosenberg, H. F. Search for Related Content PubMed PubMed Citation Articles by Rosenberg, H. F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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