CD47 knockout mice exhibit improved recovery from spinal cord injury

Autor: Scott A. Myers, William H. DeVries, Kariena R. Andres, Mark J. Gruenthal, Richard L. Benton, James B. Hoying, Theo Hagg, Scott R. Whittemore
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Neurobiology of Disease, Vol 42, Iss 1, Pp 21-34 (2011)
Druh dokumentu: article
ISSN: 1095-953X
76345130
DOI: 10.1016/j.nbd.2010.12.010
Popis: Recent data have implicated thrombospondin-1 (TSP-1) signaling in the acute neuropathological events that occur in microvascular endothelial cells (ECs) following spinal cord injury (SCI) (Benton et al., 2008b). We hypothesized that deletion of TSP-1 or its receptor CD47 would reduce these pathological events following SCI. CD47 is expressed in a variety of tissues, including vascular ECs and neutrophils. CD47 binds to TSP-1 and inhibits angiogenesis. CD47 also binds to the signal regulatory protein (SIRP)α and facilitates neutrophil diapedesis across ECs to sites of injury. After contusive SCI, TSP-1−/− mice did not show functional improvement compared to wildtype (WT) mice. CD47−/− mice, however, exhibited functional locomotor improvements and greater white matter sparing. Whereas targeted deletion of either CD47 or TSP-1 improved acute epicenter vascularity in contused mice, only CD47 deletion reduced neutrophil diapedesis and increased microvascular perfusion. An ex vivo model of the CNS microvasculature revealed that CD47−/−-derived microvessels (MVs) prominently exhibit adherent WT or CD47−/− neutrophils on the endothelial lumen, whereas WT-derived MVs do not. This implicates a defect in diapedesis mediated by the loss of CD47 expression on ECs. In vitro transmigration assays confirmed the role of SIRPα in neutrophil diapedesis through EC monolayers. We conclude that CD47 deletion modestly, but significantly, improves functional recovery from SCI via an increase in vascular patency and a reduction of SIRPα-mediated neutrophil diapedesis, rather than the abrogation of TSP-1-mediated anti-angiogenic signaling.
Databáze: Directory of Open Access Journals
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