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SUMMARYComplement (C) activation is believed to play an adverse role in several chronic degenerative disease processes, including atherosclerosis, myocardial infarction and Alzheimer's disease. We developed several in vitro quantitative assays to evaluate processes which activate C in human serum, and to assess candidates which might block that activation. Binding of C-reactive protein (CRP) to immobilized cell surfaces was used as a tissue-based method of activation, while immunoglobulin G in solution was used as a surrogate antibody method. Activation was assessed by deposition of C fragments on fixed cell surfaces, or by capture of C5b-9 from solution. We observed that several cell lines, including SH-SY5Y, U-937, THP-1 and ECV304, bound CRP and activated C following attachment of cells to a plastic surface by means of air drying. Treatment of human neuroblastoma SH-SY5Y cells with the reactive oxygen intermediates generated by xanthine (Xa) -xanthine oxidase (XaOx) prior to air drying or by hydrogen peroxide solutions after air drying, enhanced C activation, possibly through oxidation of the cell lipid membrane. Several C inhibitors were tested for their effectiveness in blocking these systems. Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1-1000 mg /ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor.

Angiotensin-converting enzyme (ACE), choline acetyltransferase and acetylcholinesterase were measured in seven cortical regions from the brains of 11 neurologically normal controls, 15 cases of dementia of the Alzheimer type, 6 cases of Parkinson dementia, and 12 cases with other neurological diseases. The groups did not differ significantly in age or postmortem delay. As expected, the cholinergic enzyme activities were significantly correlated with each other and were both markedly reduced in the Alzheimer and Parkinson dementia groups. Overall, ACE activity was not correlated with either of the cholinergic enzymes, and was not significantly affected by clinical category. The activity did, however, show significant regional variation and appeared somewhat higher in females than in males. The mean cortical ACE activity showed a statistically significant increase with age.

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