The Ly49Q Receptor Plays a Crucial Role in Neutrophil Polarization and Migration by Regulating Raft Trafficking

Shigemi Sasawatari; Mariko Yoshizaki; Choji Taya; Aya Tazawa; Kaori Furuyama-Tanaka; Hiromichi Yonekawa; Taeko Dohi; Andrew P. Makrigiannis; Takehiko Sasazuki; Kayo Inaba; Noriko Toyama-Sorimachi

doi:10.1016/j.immuni.2010.01.012

The Ly49Q Receptor Plays a Crucial Role in Neutrophil Polarization and Migration by Regulating Raft Trafficking

Shigemi Sasawatari, Mariko Yoshizaki, Choji Taya, Aya Tazawa, Kaori Furuyama-Tanaka, Hiromichi Yonekawa, Taeko Dohi, Andrew P. Makrigiannis, Takehiko Sasazuki, Kayo Inaba, Noriko Toyama-Sorimachi

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	200-213
Number of pages	14
Journal	Immunity
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2010.01.012
Publication status	Published - Feb 26 2010
Externally published	Yes

Bibliographical note

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.

ASJC Scopus Subject Areas

Immunology and Allergy
Immunology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2010.01.012

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title = "The Ly49Q Receptor Plays a Crucial Role in Neutrophil Polarization and Migration by Regulating Raft Trafficking",

abstract = "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.",

author = "Shigemi Sasawatari and Mariko Yoshizaki and Choji Taya and Aya Tazawa and Kaori Furuyama-Tanaka and Hiromichi Yonekawa and Taeko Dohi and Makrigiannis, {Andrew P.} and Takehiko Sasazuki and Kayo Inaba and Noriko Toyama-Sorimachi",

note = "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. ",

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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.

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JO - Immunity

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ER -

The Ly49Q Receptor Plays a Crucial Role in Neutrophil Polarization and Migration by Regulating Raft Trafficking

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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