Role of endogenous proteinase inhibitors in the regulation of the blood clotting system of the horseshoe crab, Limulus polyphemus.

Blood clotting in Limulus is dependent on the activity of a proteinase which converts the zymogen, coagulogen, into a form that undergoes polymerization to form the clot. The abilities of a series of recently discovered endogenous proteinase inhibitors to inhibit this enzyme and thereby serve as potential regulators of its activity were explored. The blood plasma of Limulus contains a single inhibitor that is functionally and structurally homologous to vertebrate alpha 2 macroglobulin. During exocytosis, the blood cells (amebocytes) release a series of inhibitors, including small quantities of the alpha 2 macroglobulin homologue; a low molecular weight, acid-and heat-stable inhibitor; and an acid acid-labile activity. Of the three inhibitory activities, only the cell-released, acid-labile inhibitor is capable of inhibiting the clotting enzyme.