TY - JOUR
T1 - The Ly49Q Receptor Plays a Crucial Role in Neutrophil Polarization and Migration by Regulating Raft Trafficking
AU - Sasawatari, Shigemi
AU - Yoshizaki, Mariko
AU - Taya, Choji
AU - Tazawa, Aya
AU - Furuyama-Tanaka, Kaori
AU - Yonekawa, Hiromichi
AU - Dohi, Taeko
AU - Makrigiannis, Andrew P.
AU - Sasazuki, Takehiko
AU - Inaba, Kayo
AU - Toyama-Sorimachi, Noriko
N1 - Funding Information:
We thank T. Kitamura for providing the pMxs-IRES-GFP plasmid; J. Miyazaki for the pCAGGS plasmid; M. Miyasaka, T. Sado, L.A. Miglietta, and G.E. Gray for critical reading of this manuscript; T. Okamura, S. Takahashi, and other members of JAC Inc., Japan, for animal care; and M. Ookubo, N. Sato-Yamashiro and M. Nakasuji for technical support. We also thank H. Sorimachi, K. Nishikawa, and M. Watanabe-Takahashi for helpful discussion and raft preparation and Ms. K. Furuta for secretarial support. This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (17590445 and 19590507 for N.T-S., 1839012 for K.I.), grants-in-aid for Research on intractable diseases from the Ministry of Health and Labour Sciences research grants (N.T.-S.), and grants from the Takeda Foundation and the Naito Foundation. S.S., M.Y., A.T., and K.F.-T. performed experiments; C.T. and H.Y. established Tg mice; T.D. helped in doing experiments; A.P.M. generated KO mice; and N.T.-S. designed the research and wrote the manuscript with K.I. and T.S.
PY - 2010/2/26
Y1 - 2010/2/26
N2 - Neutrophils rapidly undergo polarization and directional movement to infiltrate the sites of infection and inflammation. Here, we show that an inhibitory MHC I receptor, Ly49Q, was crucial for the swift polarization of and tissue infiltration by neutrophils. During the steady state, Ly49Q inhibited neutrophil adhesion by preventing focal-complex formation, likely by inhibiting Src and PI3 kinases. However, in the presence of inflammatory stimuli, Ly49Q mediated rapid neutrophil polarization and tissue infiltration in an ITIM-domain-dependent manner. These opposite functions appeared to be mediated by distinct use of effector phosphatase SHP-1 and SHP-2. Ly49Q-dependent polarization and migration were affected by Ly49Q regulation of membrane raft functions. We propose that Ly49Q is pivotal in switching neutrophils to their polarized morphology and rapid migration upon inflammation, through its spatiotemporal regulation of membrane rafts and raft-associated signaling molecules.
AB - Neutrophils rapidly undergo polarization and directional movement to infiltrate the sites of infection and inflammation. Here, we show that an inhibitory MHC I receptor, Ly49Q, was crucial for the swift polarization of and tissue infiltration by neutrophils. During the steady state, Ly49Q inhibited neutrophil adhesion by preventing focal-complex formation, likely by inhibiting Src and PI3 kinases. However, in the presence of inflammatory stimuli, Ly49Q mediated rapid neutrophil polarization and tissue infiltration in an ITIM-domain-dependent manner. These opposite functions appeared to be mediated by distinct use of effector phosphatase SHP-1 and SHP-2. Ly49Q-dependent polarization and migration were affected by Ly49Q regulation of membrane raft functions. We propose that Ly49Q is pivotal in switching neutrophils to their polarized morphology and rapid migration upon inflammation, through its spatiotemporal regulation of membrane rafts and raft-associated signaling molecules.
UR - http://www.scopus.com/inward/record.url?scp=76949101548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76949101548&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2010.01.012
DO - 10.1016/j.immuni.2010.01.012
M3 - Article
C2 - 20153219
AN - SCOPUS:76949101548
SN - 1074-7613
VL - 32
SP - 200
EP - 213
JO - Immunity
JF - Immunity
IS - 2
ER -
