Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury

Abstract

Following traumatic injury to the spinal cord, hematogenous inflammatory cells including neutrophils, monocytes, and lymphocytes infiltrate the lesion in a distinct temporal sequence. To examine potential mechanisms for their recruitment, we measured chemokine mRNAs in the contused rat spinal cord, using specific and sensitive reverse transcriptase polymerase chain reaction (RT-PCR) dot-blot hybridization assays. The neutrophil chemoattractant GRO-alpha was 30-fold higher than control values at 6 hr postinjury and decayed rapidly thereafter. LIX, a highly related alpha-chemokine, also was elevated early postinjury. Monocyte chemoattractant peptide (MCP)-1 and MCP-5 mRNAs, potent chemoattractants for monocytes, were significantly elevated at the lesion epicenter at 12 and 24 hr postinjury and declined thereafter. Interferon-gamma-inducible protein, 10 kDa (IP-10), chemoattractant towards activated T-lymphocytes, was significantly elevated at 6 and 12 hr postinjury. The dendritic cell chemoattractant MIP-3alpha also was increased, perhaps contributing to the development of T-cell autoreactivity to neural components after spinal cord injury (SCI) in rats. Other beta-chemokines, including MIP-1alpha and RANTES (regulated on expression normal T-cell expressed and secreted), were minimally affected by SCI. Expression of chemokines, therefore, directly precedes the influx of target neutrophils, monocytes, and T-cells into the spinal cord postinjury, as noted previously. Thus, selective chemokine expression may be integral to inflammatory processes within the injured spinal cord as a mechanism of recruitment for circulating leukocytes.

Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces secondary damage in experimental spinal cord injury

“…An acute inflammatory response characterized by neutrophil infiltration and activation of microglia develops within hours of spinal cord injury. 26 These reactive cells produce several proinflammatory cytokines including IL-1, TNFa, IL-6, IL-3 and granulocyte-macrophage colony-stimulating factor, which mediate the inFammatory response and regulate cellular events after SCI. [4][5][6] TNFa and IL-1b are significantly upregulated in the injured spinal cord as early as 1 h after SCI.…”

Pancreatitis-Associated Protein-III Is a Novel Macrophage Chemoattractant Implicated in Nerve Regeneration

“…In particular, we did not detect any induction of PAP-III expression in CNS glial cells, such as oligodendrocytes, or astrocytes in our spinal cord injury model . Conversely, MCP-1 is induced in a wide variety of traumatic damage and inflammation, including CNS injuries (Rollins, 1996;McTigue et al, 1998;Minami and Satoh, 2003). Actually, the accumulation of macrophages and/or microglial cells around an injury site is significantly delayed in the CNS (Perry et al, 1987;Perry and Gordon, 1991;Avellino et al, 1995), and subsequent removal of myelin from the injured CNS is also limited (George and Griffin, 1994;Avellino et al, 1995).…”

Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes

“…Chemokines are small, secreted molecules that have very specific conserved cysteine residues in their amino acid sequences. Chemokines are expressed early after injury and are thought to play a role in the recruitment of inflammatory cells to the lesion site (66,67) . There is a close correlation between infiltration of hematogenous cells and the expression of soluble mediators, particularly chemokines, in injured tissue.…”