TY - JOUR
T1 - The membrane attack complex of the complement system is essential for rapid wallerian degeneration
AU - Ramaglia, Valeria
AU - King, Rosalind Helen Mary
AU - Nourallah, Michelle
AU - Wolterman, Ruud
AU - de Jonge, Rosalein
AU - Ramkema, Marja
AU - Vigar, Miriam Ann
AU - van der Wetering, Sandra
AU - Morgan, Brian Paul
AU - Troost, Dirk
AU - Baas, Frank
PY - 2007
Y1 - 2007
N2 - The complement (C) system plays an important role in myelin breakdown during Wallerian degeneration (WD). The pathway and mechanism involved are, however, not clear. In a crush injury model of the sciatic nerve, we show that C6, necessary for the assembly of the membrane attack complex (MAC), is essential for rapid WD. At 3 d after injury, pronounced WD occurred in wild-type animals, whereas the axons and myelin of C6- deficient animals appeared intact. Macrophage recruitment and activation was inhibited in C6-deficient rats. However, 7 d after injury, the distal part of the C6-deficient nerves appeared degraded. As a consequence of a delayed WD, more myelin breakdown products were present than in wild-type nerves. Reconstitution of the C6-deficient animals with C6 restored the wild-type phenotype. Treatment with rhC1INH (recombinant human complement 1 inhibitor) blocked deposition of activated C-cleaved products after injury. These experiments demonstrate that the classical pathway of the complement system is activated after acute nerve trauma and that the entire complement cascade, including MAC deposition, is essential for rapid WD and efficient clearance of myelin after acute peripheral nerve trauma
AB - The complement (C) system plays an important role in myelin breakdown during Wallerian degeneration (WD). The pathway and mechanism involved are, however, not clear. In a crush injury model of the sciatic nerve, we show that C6, necessary for the assembly of the membrane attack complex (MAC), is essential for rapid WD. At 3 d after injury, pronounced WD occurred in wild-type animals, whereas the axons and myelin of C6- deficient animals appeared intact. Macrophage recruitment and activation was inhibited in C6-deficient rats. However, 7 d after injury, the distal part of the C6-deficient nerves appeared degraded. As a consequence of a delayed WD, more myelin breakdown products were present than in wild-type nerves. Reconstitution of the C6-deficient animals with C6 restored the wild-type phenotype. Treatment with rhC1INH (recombinant human complement 1 inhibitor) blocked deposition of activated C-cleaved products after injury. These experiments demonstrate that the classical pathway of the complement system is activated after acute nerve trauma and that the entire complement cascade, including MAC deposition, is essential for rapid WD and efficient clearance of myelin after acute peripheral nerve trauma
U2 - https://doi.org/10.1523/JNEUROSCI.5623-06.2007
DO - https://doi.org/10.1523/JNEUROSCI.5623-06.2007
M3 - Article
C2 - 17634361
SN - 0270-6474
VL - 27
SP - 7663
EP - 7672
JO - Journal of neuroscience
JF - Journal of neuroscience
IS - 29
ER -