ADAM17-deficiency on Microglia but Not on Macrophages Promotes Phagocytosis and Functional Recovery After Spinal Cord Injury

Brain Behav Immun. 2019 Aug;80:129-145. doi: 10.1016/j.bbi.2019.02.032. Epub 2019 Mar 6.


A disintegrin and metalloproteinase 17 (ADAM17) is the major sheddase involved in the cleavage of a plethora of cytokines, cytokine receptors and growth factors, thereby playing a substantial role in inflammatory and regenerative processes after central nervous system trauma. By making use of a hypomorphic ADAM17 knockin mouse model as well as pharmacological ADAM10/ADAM17 inhibitors, we showed that ADAM17-deficiency or inhibition significantly increases clearance of apoptotic cells, promotes axon growth and improves functional recovery after spinal cord injury (SCI) in mice. Microglia-specific ADAM17-knockout (ADAM17flox+/+-Cx3Cr1 Cre+/-) mice also showed improved functional recovery similar to hypomorphic ADAM17 mice. In contrast, endothelial-specific (ADAM17flox+/+-Cdh5Pacs Cre+/-) and macrophage-specific (ADAM17flox+/+-LysM Cre+/-) ADAM17-knockout mice or bone marrow chimera with transplanted ADAM17-deficient macrophages, displayed no functional improvement compared to wild type mice. These data indicate that ADAM17 expression on microglia cells (and not on macrophages or endothelial cells) plays a detrimental role in inflammation and functional recovery after SCI.

Keywords: ADAM17; Inflammation; Macrophages; Microglia; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM17 Protein / metabolism*
  • Animals
  • Disease Models, Animal
  • Female
  • Inflammation / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Phagocytosis / immunology
  • Phagocytosis / physiology
  • Recovery of Function / physiology
  • Spinal Cord Injuries / metabolism*


  • ADAM17 Protein
  • Adam17 protein, mouse