Metabolism and distribution of the virus-encoded serine proteinase inhibitor SERP-1 in healthy rabbits

SERP-1 is a secreted myxoma virus-encoded 55-kd protein of the serine prote inase inhibitor ("serpin") family that strongly inhibits the mitosis of med ial arterial smooth muscle cells, thus preventing stenosis in injured rabbi t and rat arteries. We have measured the fractional catabolic rate (FCR) an d compartmental distribution of I-125-SERP-1 after injection of various dos es into the circulation of healthy rabbits. The FCR within the intravascula r space decreased from 2.99 d(-1) to 2.39 d(-1) and the whole-body FCR decr eased from 0.66 d(-1) to 0.51 d(-1) as the dose was increased 35-fold from 0.11 mug/kg to 3.8 mug/kg. The fractional distribution of SERP-1 between th e intravascular (0.21), noncirculating vascular wall t0.09), and extravascu lar compartments (0.70) at equilibrium did not change significantly over th is dose range. SERP-1 did not appear to selectively accumulate in any organ in any of 11 rabbits studied over a 6-day interval. In comparison to other rabbit plasma serpins, the behavior of SERP-1 in vivo most closely resembl ed that of heparin cofactor II. Copyright (C) 2000 by W.B. Saunders Company .