Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody

Systemic injection of antibodies against acetylcholinesterase (AChE) induce s complement-mediated destruction of preganglionic nerve terminals in parav ertebral sympathetic ganglia, but spares other AChE-rich structures, such a s nerve terminals in prevertebral sympathetic ganglia, parasympathetic gang lia, and the neuromuscular junction. This pattern of differing sensitivity to "AChE immunolesion" might be explained by a differing expression of prot eins that serve to protect host cells from complement activation. Two major complement regulatory proteins in rats are Crry, which interferes with the assembly of C3 convertase, and CD59, which blocks formation of the termina l cytolytic membrane attack complex. The present study used immunohistochem istry to demonstrate an inverse relation between levels of CD59 and Crry ex pression and sensitivity to AChE immunolesion in several AChE-rich targets. Thus, the most sensitive structures, i.e., preganglionic nerve terminals i n the adrenal gland and superior cervical ganglion (SCG), expressed undetec table levels of CD59 and Crry immunoreactivities. By contrast, AChE-rich, b ut antibody-resistant, cholinergic nerve terminals in the inferior mesenter ic ganglia (IMG) and diaphragm muscle expressed significant amounts of CD59 and Crry. Such expression was functionally important because, after membra ne-anchored CD59 was removed from explanted IMG with phosphatidylinositol p hospholipase C, exposure to AChE antibody and complement caused greater imm unolesion. It was concluded that differential expression of regulatory prot eins in different parts of the nervous system influences regional vulnerabi lity to complement mediated damage. (C) 2001 Elsevier Science B.V. All righ ts reserved.