Upregulation of p55 and p75 receptors mediating TNF-α transport across the injured blood-spinal cord barrier

Authors: Pan, Weihong¹; Csernus, Balazs²; Kastin, Abba²

Source: Journal of Molecular Neuroscience, Volume 21, Number 2, June 2003 , pp. 173-184(12)

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Abstract:

Tumor necrosis factor (TNF-α) is involved in the inflammation and tissue regeneration occurring after spinal cord injury (SCI). This study tests the specific role of p55 and p75 receptors in mediating the transport of TNF-α across the blood-spinal cord barrier (BSCB) after SCI by compression. Transcytosis of ¹²⁵I-TNF-α across a monolayer of the cerebral endothelial cells that compose the blood-brain barrier was significantly reduced in the absence of functional p55 and p75 receptors. At 3 d after SCI, double receptor knockout mice had a significantly reduced increase in TNF-α uptake from blood to injured lumbar spinal cord as compared with their inbred controls, despite the similar extent of BSCB disruption (measured by ^99mTc-albumin). The p75 single receptor knockout mice had a reduced increase in ¹²⁵I-TNF-α uptake, whereas the p55 receptor knockout mice had no significant increase of ¹²⁵I-TNF-α uptake after SCI, suggesting that the p55 receptor plays a major role. Hence, the increased uptake of TNF-α 3 d after SCI is not explained by nonspecific barrier disruption but by receptor-mediated upregulation of transport. Quantitative RT-PCR analysis further showed that upregulation of TNF-α transport was related to increased expression of mRNA for p55 and p75 receptors. The increase of p55 receptor expression was more robust and seen between 12 h and 1 wk after SCI, whereas the increase of p75 receptor expression occurred later and involved fewer regions. Thus, the differential upregulation of p55 and p75 receptors indicates that permeation of TNF-α across the injured BSCB remains a regulated process. Knowledge of receptor-mediated regulation could facilitate effective therapeutic manipulation of BSCB permeation of vascular cytokines important to CNS regeneration.

Keywords: TNF-α; receptor; SCI; transport; neuroregeneration; spinal cord; blood-brain barrier

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:21:2:173

Affiliations: 1: Department of Medicine, Tulane University Health Science Center and the VA Medical Center, 70112-1262, New Orleans, Louisiana, Email: wpan@tulane.edu 2: Department of Medicine, Tulane University Health Science Center and the VA Medical Center, 70112-1262, New Orleans, Louisiana,

Publication date: 2003-06-01

Upregulation of p55 and p75 receptors mediating TNF-α transport across the injured blood-spinal cord barrier

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