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 proteinase inhibitor ("serpin") family that strongly inhibits the mitosis of medial arterial smooth muscle cells, thus preventing stenosis in injured rabbit and rat arteries. We have measured the fractional catabolic rate (FCR) and compartmental distribution of 1251-SERP-1 after injection of various doses into the circulation of healthy rabbits. The FCR within the intravascular space decreased from 2.99 d(-1) to 2.39 d(-1) and the whole-body FCR decreased from 0.66 d(-1) to 0.51 d(-1) as the dose was increased 35-fold from 0.11 microg/kg to 3.8 microg/kg. The fractional distribution of SERP-1 between the intravascular (0.21), noncirculating vascular wall (0.09), and extravascular compartments (0.70) at equilibrium did not change significantly over this 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 resembled that of heparin cofactor II.