Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes

Youngrok Park, Joon Lee, Jae Yong Kwak, Kyoungmi Noh, Eunjung Yim, Hyun Kyung Kim, Young June Kim, Hal Broxmeyer, Jeong A. Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)53-66
Number of pages14
JournalJournal of Leukocyte Biology
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Chemokine CX3CL1
Monocytes
Muscles
Bone Marrow
Macrophages
Chemotaxis
Perfusion
Platelet Factor 4
Therapeutic Uses
Thigh
Vascular Endothelial Growth Factor A
Extremities

Keywords

  • Angiogenesis
  • CX3CL1
  • CX3CR1
  • Monocyte

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Park, Y., Lee, J., Kwak, J. Y., Noh, K., Yim, E., Kim, H. K., ... Kim, J. A. (2018). Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes. Journal of Leukocyte Biology, 103(1), 53-66. https://doi.org/10.1189/jlb.1A0117-002RR

Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes. / Park, Youngrok; Lee, Joon; Kwak, Jae Yong; Noh, Kyoungmi; Yim, Eunjung; Kim, Hyun Kyung; Kim, Young June; Broxmeyer, Hal; Kim, Jeong A.

In: Journal of Leukocyte Biology, Vol. 103, No. 1, 01.01.2018, p. 53-66.

Research output: Contribution to journalArticle

Park, Y, Lee, J, Kwak, JY, Noh, K, Yim, E, Kim, HK, Kim, YJ, Broxmeyer, H & Kim, JA 2018, 'Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes', Journal of Leukocyte Biology, vol. 103, no. 1, pp. 53-66. https://doi.org/10.1189/jlb.1A0117-002RR
Park, Youngrok ; Lee, Joon ; Kwak, Jae Yong ; Noh, Kyoungmi ; Yim, Eunjung ; Kim, Hyun Kyung ; Kim, Young June ; Broxmeyer, Hal ; Kim, Jeong A. / Fractalkine induces angiogenic potential in CX3CR1-expressing monocytes. In: Journal of Leukocyte Biology. 2018 ; Vol. 103, No. 1. pp. 53-66.
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AB - 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.

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