Ligation of the adhesion-GPCR EMR2 regulates human neutrophil function.
At present, approximately 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 proinflammatory mediators and show that the transmembrane region is critical for adhesion-GPCR function. Using an anti-EMR2 antibody, ligation of EMR2 increases neutrophil 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
Simon
S
Sir William Dunn School of Pathology, Oxford University, Oxford, OX1 3RE, UK.
Lin
Hsi-Hsien
HH
Dri
Pietro
P
Davies
John Q
JQ
Hayhoe
Richard P G
RP
Lewis
Sion M
SM
Heinsbroek
Sigrid E M
SE
Brown
K Alun
KA
Perretti
Mauro
M
Hamann
Jörg
J
Treacher
David F
DF
Gordon
Siamon
S
Stacey
Martin
M
D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D006801:Humans; D051379:Mice; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation
C412456:ADGRE2 protein, human; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides