Immunosympathectomy: lack of evidence for a complement-mediated cytotoxic mechanism.
To determine whether the destruction of peripheral sympathetic neurons by anti-NGF-antibodies results from a complement-mediated cytotoxic action or from the deprivation of endogenous NGF or immunologically NGF-like cross-reacting molecules we investigated the time-course of the reversibility of the effect of NGF-antibodies by neutralizing doses of NGF, together with the effect of NGF-antibodies in complement-deficient mice. After administration of a single dose of 50 mg/kg of purified antibodies to newborn rats the TH level was reduced to 75% of controls after 12 h, to 48% after 24 h, 39% after 36, and 28% after 48 h. After this time no further reduction occurred and levels remained constant up to 14 days. The effect of the NGF-antibodies was reversible on addition of NGF up to 48 h after antibody administration. Although the reversibility was not complete (85% of controls) the extent of the reversibility was the same whether NGF was given 12 or 48 h after the antibodies. The incompleteness of the reversibility is reflected by the small number of degenerating neurons apparent as early as 12 h after antibody administration. Since these early degenerative effects were also seen in complement-deficient mice it is concluded that they involve a small population of neurons, sensitive to short-term NGF deprivation whereas the majority of the neurons can withstand deprivation for up to 48 h without sustaining irreversible damage.
D000320:Adrenergic Fibers / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D003182:Complement C5 / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005728:Ganglia, Sympathetic / Q000201:enzymology; D051379:Mice; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000276:immunology; D010870:Pineal Gland / Q000201:enzymology; D051381:Rats; D013363:Submandibular Gland / Q000201:enzymology / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000906:Antibodies; D003182:Complement C5; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase