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Ligation of the adhesion‐GPCR EMR2 regulates human neutrophil function
Author(s) -
Yona Simon,
Lin HsiHsien,
Dri Pietro,
Davies John Q.,
Hayhoe Richard P. G.,
Lewis Sion M.,
Heinsbroek Sigrid E. M.,
Brown K. Alun,
Perretti Mauro,
Hamann Jorg,
Treacher David F.,
Gordon Siamon,
Stacey Martin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-9435com
Subject(s) - microbiology and biotechnology , g protein coupled receptor , innate immune system , cell adhesion , proinflammatory cytokine , receptor , inflammation , adhesion , biology , signal transduction , chemistry , immunology , biochemistry , organic chemistry
At present, ~150 different members of the adhesion‐G protein‐coupled receptor (GPCR) family have been identified in metazoans. Surprisingly, very little is known about their function, although they all possess large extracellular domains coupled to a seven‐transmembrane domain, suggesting a potential role in cell adhesion and signaling. Here, we demonstrate how the human‐restricted adhesion‐GPCR, EMR2 (epidermal growth factor‐like module‐containing mucin‐like hormone receptor), regulates neutrophil responses by potentiating the effects of a number of proinflamma‐tory mediators and show that the transmembrane region is critical for adhesion‐GPCR function. Using an anti‐EMR2 antibody, ligation of EMR2 increases neu‐trophil adhesion and migration, and augments superoxide production and proteolytic enzyme degranulation. On neutrophil activation, EMR2 is rapidly translocated to membrane ruffles and the leading edge of the cell. Further supporting the role in neutrophil activation, EMR2 expression on circulating neutrophils is significantly increased in patients with systemic inflammation. These data illustrate a definitive function for a human adhesion‐GPCR within the innate immune system and suggest an important role in potentiating the inflammatory response. Ligation of the adhesion‐GPCR EMR2 regulates human neutrophil function.—Yona S., Lin, H.‐H., Dri, P., Davies, J. Q., Hayhoe, R. P. G., Lewis, S. M., Heinsbroek, S. E. M., Brown, K. A., Perretti, M., Hamann, J., Treacher, D. F., Gordon S., Stacey M. Ligation of the adhesion‐GPCR EMR2 regulates human neutrophil function. FASEB J . 22, 741–751 (2008)