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Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow

หน่วยงาน Nanyang Technological University, Singapore

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ชื่อเรื่อง : Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow
นักวิจัย : Devi, Sapna , Wang, Yilin , Chew, Weng Keong , Lima, Ronald , A-González, Noelia , Mattar, Citra N. Z. , Chong, Shu Zhen , Schlitzer, Andreas , Bakocevic, Nadja , Chew, Samantha , Keeble, Jo L. , Goh, Chi Ching , Li, Jackson L. Y. , Evrard, Maximilien , Malleret, Benoit , Larbi, Anis , Renia, Laurent , Haniffa, Muzlifah , Tan, Suet Mien , Chan, Jerry K. Y. , Balabanian, Karl , Nagasawa, Takashi , Bachelerie, Françoise , Hidalgo, Andrés , Ginhoux, Florent , Kubes, Paul , Ng, Lai Guan
คำค้น : DRNTU::Science::Medicine
หน่วยงาน : Nanyang Technological University, Singapore
ผู้ร่วมงาน : -
ปีพิมพ์ : 2556
อ้างอิง : Devi, S., Wang, Y., Chew, W. K., Lima, R., A-González, N., Mattar, C. N. Z., & et al. (2013). Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. Journal of experimental medicine, 210(11), 2321-2336. , 0022-1007 , http://hdl.handle.net/10220/25057 , http://dx.doi.org/10.1084/jem.20130056
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : Journal of experimental medicine
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Blood neutrophil homeostasis is essential for successful host defense against invading pathogens. Circulating neutrophil counts are positively regulated by CXCR2 signaling and negatively regulated by the CXCR4–CXCL12 axis. In particular, G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been shown to correct neutropenia in human patients. G-CSF directly induces neutrophil mobilization from the bone marrow (BM) into the blood, but the mechanisms underlying plerixafor-induced neutrophilia remain poorly defined. Using a combination of intravital multiphoton microscopy, genetically modified mice and novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via plerixafor does not result in neutrophil mobilization from the BM. Instead, plerixafor augments the frequency of circulating neutrophils through their release from the marginated pool present in the lung, while simultaneously preventing neutrophil return to the BM. Our study demonstrates for the first time that drastic changes in blood neutrophils can originate from alternative reservoirs other than the BM, while implicating a role for CXCR4–CXCL12 interactions in regulating lung neutrophil margination. Collectively, our data provides valuable insights into the fundamental regulation of neutrophil homeostasis, which may lead to the development of improved treatment regimens for neutropenic patients.

บรรณานุกรม :
Devi, Sapna , Wang, Yilin , Chew, Weng Keong , Lima, Ronald , A-González, Noelia , Mattar, Citra N. Z. , Chong, Shu Zhen , Schlitzer, Andreas , Bakocevic, Nadja , Chew, Samantha , Keeble, Jo L. , Goh, Chi Ching , Li, Jackson L. Y. , Evrard, Maximilien , Malleret, Benoit , Larbi, Anis , Renia, Laurent , Haniffa, Muzlifah , Tan, Suet Mien , Chan, Jerry K. Y. , Balabanian, Karl , Nagasawa, Takashi , Bachelerie, Françoise , Hidalgo, Andrés , Ginhoux, Florent , Kubes, Paul , Ng, Lai Guan . (2556). Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow.
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Devi, Sapna , Wang, Yilin , Chew, Weng Keong , Lima, Ronald , A-González, Noelia , Mattar, Citra N. Z. , Chong, Shu Zhen , Schlitzer, Andreas , Bakocevic, Nadja , Chew, Samantha , Keeble, Jo L. , Goh, Chi Ching , Li, Jackson L. Y. , Evrard, Maximilien , Malleret, Benoit , Larbi, Anis , Renia, Laurent , Haniffa, Muzlifah , Tan, Suet Mien , Chan, Jerry K. Y. , Balabanian, Karl , Nagasawa, Takashi , Bachelerie, Françoise , Hidalgo, Andrés , Ginhoux, Florent , Kubes, Paul , Ng, Lai Guan . 2556. "Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow".
    กรุงเทพมหานคร : Nanyang Technological University, Singapore.
Devi, Sapna , Wang, Yilin , Chew, Weng Keong , Lima, Ronald , A-González, Noelia , Mattar, Citra N. Z. , Chong, Shu Zhen , Schlitzer, Andreas , Bakocevic, Nadja , Chew, Samantha , Keeble, Jo L. , Goh, Chi Ching , Li, Jackson L. Y. , Evrard, Maximilien , Malleret, Benoit , Larbi, Anis , Renia, Laurent , Haniffa, Muzlifah , Tan, Suet Mien , Chan, Jerry K. Y. , Balabanian, Karl , Nagasawa, Takashi , Bachelerie, Françoise , Hidalgo, Andrés , Ginhoux, Florent , Kubes, Paul , Ng, Lai Guan . "Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow."
    กรุงเทพมหานคร : Nanyang Technological University, Singapore, 2556. Print.
Devi, Sapna , Wang, Yilin , Chew, Weng Keong , Lima, Ronald , A-González, Noelia , Mattar, Citra N. Z. , Chong, Shu Zhen , Schlitzer, Andreas , Bakocevic, Nadja , Chew, Samantha , Keeble, Jo L. , Goh, Chi Ching , Li, Jackson L. Y. , Evrard, Maximilien , Malleret, Benoit , Larbi, Anis , Renia, Laurent , Haniffa, Muzlifah , Tan, Suet Mien , Chan, Jerry K. Y. , Balabanian, Karl , Nagasawa, Takashi , Bachelerie, Françoise , Hidalgo, Andrés , Ginhoux, Florent , Kubes, Paul , Ng, Lai Guan . Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. กรุงเทพมหานคร : Nanyang Technological University, Singapore; 2556.