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Fractalkine induces angiogenic potential in CX3CR1‐expressing monocytes
Author(s) -
Park Youngrok,
Lee Joon,
Kwak JaeYong,
Noh Kyoungmi,
Yim Eunjung,
Kim HyunKyung,
Kim Young June,
Broxmeyer Hal E.,
Kim JeongA.
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1a0117-002rr
Subject(s) - biology , cx3cr1 , monocyte , microbiology and biotechnology , chemokine , immunology , cancer research , inflammation , chemokine receptor
We report the unique role of CX3CL1 (or fractalkine) on CD11b + myelomonocytic cells expressing CX3CR1, the only known receptor for CX3CL1, in promoting blood perfusion recovery. In a mouse ischemic hind‐limb model, CD11b + CX3CR1 + cells migrated to ischemic femoral muscles through CX3CL1‐mediated chemotaxis. CD11b + CX3CR1 + macrophages isolated from ischemic tissues [tissue (T)‐CD11b + CX3CR1 + ] of muscle exert a proangiogenic effect through platelet factor‐4 (CXCL4; PF‐4) production. PF‐4 does not promote angiogenesis by itself but, instead, increases VEGF‐mediated angiogenesis. Despite proangiogenic effects of muscle‐derived T‐CD11b + CX3CR1 + macrophages, their clinical implementation is limited because muscle excision is required for cell harvesting. Therefore, we focused on the more accessible bone marrow (BM)‐CD11b + CX3CR1 + monocytes, which migrate from BM into ischemic muscles via CX3CL1‐mediated chemotaxis. PF‐4 expression was not detected in BM‐CD11b + CX3CR1 + monocytes under normal conditions, but CX3CL1 (50 ng/ml) induced high PF‐4 expression and enabled BM‐CD11b + CX3CR1 + monocytes to achieve a similar angiogenic potential to that of T‐CD11b + CX3CR1 + macrophages ex vivo. Furthermore, we were able to identify a subset of monocytes that express CD11b and CX3CR1 in human peripheral blood and confirmed the proangiogenic effect of CX3CL1 treatment. Thus, CX3CL1‐treated CD11b + CX3CR1 + monocytes may be of potential therapeutic use to significantly accelerate recovery of blood perfusion in ischemic diseases.