Upregulation of complement inhibitors in association with vulnerable cells following contusion-induced spinal cord injury.
We have previously described the activation of the classical, alternative, and terminal complement cascade pathways after acute contusion spinal cord injury using the New York University (NYU) weight-drop impactor. In the present study, we examined the induction of protein regulators of the complement cascade, factor H (FH), and clusterin, in the same experimental paradigm. The spinal cord of laminectomized adult rats was subjected to mild or severe injury using impactor weight-drop heights of 12.5 and 50 mm, respectively. The spinal cords of control and injured animals were evaluated at 1, 7, and 42 days after injury. Immunocytochemistry revealed a robust increase in the numbers and intensity of staining of FH, and clusterin-positive cells in the injured cord at all three time points, with the highest increases observed at 1 and 42 days after injury. FH and clusterin-positive cells were observed among neurons as well as oligodendrocytes. The increased expression was detected both rostrally and caudally from the injury site, in the latter case at distances up to 20 mm. The precise biological significance of injury-induced upregulation of these proteins remains to be determined. However, FH and clusterin are potent regulators of complement activity targeting upstream (FH) and downstream (clusterin) molecules of the pro-inflammatory cascade, which could be of vital importance in preventing a "runaway" inflammatory reaction in the injured spinal cord.
Anderson
Aileen J
AJ
Department of Physical Medicine and Rehabilitation, and the Reeve-Irvine Center, University of California, Irvine, California, USA. aja@uci.edu
Najbauer
Joseph
J
Huang
Wencheng
W
Young
Wise
W
Robert
Stephanie
S
D000818:Animals; D003169:Complement Inactivator Proteins / Q000096:biosynthesis*; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013904:Thoracic Vertebrae; D015854:Up-Regulation / Q000502:physiology*
D003169:Complement Inactivator Proteins