Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody.
Systemic injection of antibodies against acetylcholinesterase (AChE) induces complement-mediated destruction of preganglionic nerve terminals in paravertebral sympathetic ganglia, but spares other AChE-rich structures, such as nerve terminals in prevertebral sympathetic ganglia, parasympathetic ganglia, and the neuromuscular junction. This pattern of differing sensitivity to "AChE immunolesion" might be explained by a differing expression of proteins 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 terminal cytolytic membrane attack complex. The present study used immunohistochemistry to demonstrate an inverse relation between levels of CD59 and Crry expression and sensitivity to AChE immunolesion in several AChE-rich targets. Thus, the most sensitive structures, i.e., preganglionic nerve terminals in the adrenal gland and superior cervical ganglion (SCG), expressed undetectable levels of CD59 and Crry immunoreactivities. By contrast, AChE-rich, but antibody-resistant, cholinergic nerve terminals in the inferior mesenteric ganglia (IMG) and diaphragm muscle expressed significant amounts of CD59 and Crry. Such expression was functionally important because, after membrane-anchored CD59 was removed from explanted IMG with phosphatidylinositol phospholipase C, exposure to AChE antibody and complement caused greater immunolesion. It was concluded that differential expression of regulatory proteins in different parts of the nervous system influences regional vulnerability to complement mediated damage.
Department of Pharmacology, Mayo Clinic, 727 Guggenheim Building, Rochester, MN 55905, USA. tang.hui@mayo.edu
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D000110:Acetylcholinesterase / Q000276:immunology; D000311:Adrenal Glands / Q000294:innervation; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000954:Antigens, Surface; D018957:CD59 Antigens / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D017729:Presynaptic Terminals / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013563:Sympathectomy, Chemical; D010738:Type C Phospholipases / Q000378:metabolism
D000906:Antibodies; D000954:Antigens, Surface; D018957:CD59 Antigens; C513105:Cr1l protein, rat; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D003165:Complement System Proteins; D000110:Acetylcholinesterase; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase