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

Autor: McCreedy DA; Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, College Station, TX, 77843, USA. dmccreedy@bio.tamu.edu.; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA. dmccreedy@bio.tamu.edu.; Department of Laboratory Medicine and Immunology Program, University of California, San Francisco, CA, 94143, USA. dmccreedy@bio.tamu.edu., Abram CL; Department of Laboratory Medicine and Immunology Program, University of California, San Francisco, CA, 94143, USA., Hu Y; Department of Laboratory Medicine and Immunology Program, University of California, San Francisco, CA, 94143, USA., Min SW; Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, College Station, TX, 77843, USA., Platt ME; Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, College Station, TX, 77843, USA., Kirchhoff MA; Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, College Station, TX, 77843, USA., Reid SK; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, 77843, USA., Jalufka FL; Department of Biology, Texas A&M University, 301 Old Main Dr, ILSB 3128, College Station, TX, 77843, USA., Lowell CA; Department of Laboratory Medicine and Immunology Program, University of California, San Francisco, CA, 94143, USA.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2021 Dec 24; Vol. 18 (1), pp. 302. Date of Electronic Publication: 2021 Dec 24.
DOI: 10.1186/s12974-021-02353-2
Abstrakt: Background: Spinal 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.
Methods: Contusive spinal cord injury was performed at thoracic vertebra level 9 in mice with conditional deletion of Syk in neutrophils (Syk f/f MRP8-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.
Results: Syk 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.
Conclusions: Syk 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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