Spleen tyrosine kinase facilitates neutrophil activation and worsens long-term neurologic deficits after spinal cord injury

Journal of Neuroinflammation

Madison E. Platt¹  Sun Won Min¹  Megan A. Kirchhoff¹  Frank L. Jalufka¹  Dylan A. McCreedy²  Yongmei Hu³  Clifford A. Lowell³  Clare L. Abram³  Shelby K. Reid⁴ 

[1] Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, 77843, College Station, TX, USA;Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, 77843, College Station, TX, USA;Texas A&M Institute for Neuroscience, Texas A&M University, 77843, College Station, TX, USA;Department of Laboratory Medicine and Immunology Program, University of California, 94143, San Francisco, CA, USA;Department of Laboratory Medicine and Immunology Program, University of California, 94143, San Francisco, CA, USA;Texas A&M Institute for Neuroscience, Texas A&M University, 77843, College Station, TX, USA;

关键词: Spinal cord injury;    Neutrophils;    Inflammation;    Apoptosis;    Cytokines;    Degranulation;    Neutrophil extracellular traps;   

DOI  :  10.1186/s12974-021-02353-2

来源: Springer

【 摘 要 】

BackgroundSpinal cord injury elicits widespread inflammation that can exacerbate long-term neurologic deficits. Neutrophils are the most abundant immune cell type to invade the spinal cord in the early acute phase after injury, however, their role in secondary pathogenesis and functional recovery remains unclear. We have previously shown that neutrophil functional responses during inflammation are augmented by spleen tyrosine kinase, Syk, a prominent intracellular signaling enzyme. In this study, we evaluated the contribution of Syk towards neutrophil function and long-term neurologic deficits after spinal cord injury.MethodsContusive spinal cord injury was performed at thoracic vertebra level 9 in mice with conditional deletion of Syk in neutrophils (Sykf/fMRP8-Cre). Hindlimb locomotor recovery was evaluated using an open-field test for 35 days following spinal cord injury. Long-term white matter sparing was assessed using eriochrome cyanide staining. Blood-spinal cord barrier disruption was evaluated by immunoblotting. Neutrophil infiltration, activation, effector functions, and cell death were determined by flow cytometry. Cytokine and chemokine expression in neutrophils was assessed using a gene array.ResultsSyk deficiency in neutrophils improved long-term functional recovery after spinal cord injury, but did not promote long-term white matter sparing. Neutrophil activation, cytokine expression, and cell death in the acutely injured spinal cord were attenuated by the genetic loss of Syk while neutrophil infiltration and effector functions were not affected. Acute blood-spinal cord barrier disruption was also unaffected by Syk deficiency in neutrophils.ConclusionsSyk facilitates specific neutrophil functional responses to spinal cord injury including activation, cytokine expression, and cell death. Long-term neurologic deficits are exacerbated by Syk signaling in neutrophils independent of acute blood-spinal cord barrier disruption and long-term white matter sparing. These findings implicate Syk in pathogenic neutrophil activities that worsen long-term functional recovery after spinal cord injury.

【 授权许可】

CC BY