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  4. Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury

Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury

Journal of Neuroinflammation, 2008 · DOI: 10.1186/1742-2094-5-26 · Published: June 25, 2008

Spinal Cord InjuryImmunology

Simple Explanation

The complement system can affect the central nervous system (CNS) by regulating physiological events. After a traumatic CNS injury, complement activation can lead to the formation of C5b-9 membrane attack complex (C5b-9/MAC), potentially lysing cells. Infiltrating immune cells, specifically polymorphonuclear leukocytes (PMNs), might serve as a local source of complement post-injury. PMNs are among the first immune cells to reach the CNS after injury. This study characterizes the early and terminal complement proteins associated with PMNs both in vitro and in vivo following spinal cord injury (SCI), suggesting PMNs play a role in complement delivery and activation in the post-SCI environment.

Study Duration
42 days
Participants
Adult female Sprague Dawley rats
Evidence Level
Not specified

Key Findings

  • 1
    Stimulated or unstimulated PMNs expressed mRNAs encoding for C1q, C3, and C4, but not C5, C6, C7 or C9 in culture. Complement protein C1q or C3 was also detected in less than 30% of cultured PMNs.
  • 2
    Over 70% of PMNs infiltrating the injured spinal cord were associated with C1q, C3, C7, and C5b-9/MAC three days post-SCI, with C7 and C5b-9/MAC localized to granular vesicles within PMNs at the spinal cord epicenter.
  • 3
    PMNs were observed in the injured spinal cord for weeks post-SCI, suggesting a chronic influence on complement-mediated events and SCI pathogenesis after trauma.

Research Summary

This study investigates the expression of complement mRNAs and the presence of complement proteins associated with polymorphonuclear leukocytes (PMNs) after spinal cord injury (SCI). Cultured PMNs express mRNAs for early complement proteins (C1q, C3, C4) but not terminal proteins (C5, C6, C7, C9). However, infiltrating PMNs in the injured spinal cord are associated with both early and terminal complement proteins. The findings suggest PMNs play a role in the local internalization or deliverance of complement and its activation in the post-SCI environment, potentially influencing SCI pathogenesis.

Practical Implications

Targeted Therapies

Modulating PMN activity or complement pathways associated with PMNs may offer therapeutic strategies for SCI.

Understanding SCI Pathogenesis

Elucidating the role of PMNs in complement-mediated events contributes to a better understanding of SCI pathogenesis.

Drug Delivery

PMNs could potentially be utilized as delivery vehicles for complement-related therapeutics in SCI treatment.

Study Limitations

  • 1
    The study focuses on rat models, and findings may not directly translate to human SCI.
  • 2
    The specific mechanisms of PMN complement internalization and delivery remain to be fully elucidated.
  • 3
    The long-term consequences of PMN-mediated complement activity in SCI require further investigation.

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