Ablation of the Integrin CD11b Mac-1 Limits Deleterious Responses to Traumatic Spinal Cord Injury and Improves Functional Recovery in Mice

Yun Li; Zhuofan Lei; Rodney M. Ritzel; Junyun He; Simon Liu; Li Zhang; Junfang Wu

doi:10.3390/cells13181584

Cells (Sep 2024)

Ablation of the Integrin CD11b Mac-1 Limits Deleterious Responses to Traumatic Spinal Cord Injury and Improves Functional Recovery in Mice

Yun Li,
Zhuofan Lei,
Rodney M. Ritzel,
Junyun He,
Simon Liu,
Li Zhang,
Junfang Wu

Affiliations

Yun Li: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA
Zhuofan Lei: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA
Rodney M. Ritzel: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA
Junyun He: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA
Simon Liu: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA
Li Zhang: Department of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Junfang Wu: Department of Anesthesiology and Center for Shock, Trauma and Anesthesiology Research (STAR), University of Maryland School of Medicine, 685 W. Baltimore Street, MSTF, Room 6-034D, Baltimore, MD 21201, USA

DOI: https://doi.org/10.3390/cells13181584
Journal volume & issue: Vol. 13, no. 18
p. 1584

Abstract

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Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of CD11b mRNA starting from 1 d after injury, which persisted up to 28 d. CD11b knockout (KO) mice and their wildtype littermates were subjected to moderate SCI. At 1 d post-injury, qPCR showed increased expression of genes involved with inflammation-resolving processes in CD11b KO mice. Flow cytometry analysis of CD45intLy6C−CX3CR1+ microglia, CD45hiLy6C+Ly6G− monocytes, and CD45hiLy6C+Ly6G+ neutrophils revealed significantly reduced cell counts as well as reactive oxygen species (ROS) production in CD11b KO mice at d3 post-injury. Further examination with NanoString and RNA-seq showed upregulation of pro-inflammatory genes, but downregulation of the ROS pathway. Importantly, CD11b KO mice exhibited significantly improved locomotor function, reduced cutaneous mechanical/thermal hypersensitivity, and limited tissue damage at 8 weeks post-injury. Collectively, our data suggest an important role for CD11b in regulating tissue inflammation and functional outcome following SCI.

Published in Cells

ISSN: 2073-4409 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Cytology
Website: https://www.mdpi.com/journal/cells

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