Acute phase reactants ceruloplasmin and haptoglobin and their relationship to plasma prostaglandins in rabbits bearing the VS2 carcinoma.

Abstract

Results of a series of studies on the cause of the hypercalcemia that occurs in mice bearing the HSDM~ fibrosarcoma (1-6) and in rabbits carrying the VX2 carcinoma (7-9) have led us to conclude that these two tumors synthesize and secrete large amounts of prostaglandin E2 (PGE2) into plasma. ~ PGE~ is a potent bone resorption-stimulating agent in vitro (2, 10), and this prostaglandin and its metabolites are found in elevated concentrations in the plasma of tumor-bearing animals (2,3,(6)(7)(8)11). Because of the rapid clearance and metabolism of PGE2, measurements in plasma of the metabolite, 13,14-dihydro-15-keto-PGE2(PGE2-M), give a more accurate estimate of PGE~ secretion than do measurements of the primary prostaglandin itself (6,8,11,12). Studies on the time-course of the development of elevated plasma calcium concentrations and hyperprostaglandinemia, as well as investigations using two inhibiters of prostaglandin synthesis, indomethacin (1-3, 7) and hydrocortisone (6,8,13), support the hypothesis that the hypercalcemic syndrome in these tumor-bearing animals is due to the secretion of PGE2 by the tumor. A similar pathophysiologic mechanism may explain in part the hypercalcemia that occurs in certain patients with cancer (14-16).The present investigation was initiated because of the observation that the plasma from rabbits bearing the VX~ carcinoma became faintly blue about I wk after tumor implantation, and this color increased markedly and became intense by 3-4 wk. The time-course of the appearance and increase in the blue color in plasma was similar to that which we had previously noted for PGEz-M. We therefore undertook to identify the blue material in plasma and to examine the relationship of its increase to prostaglandin metabolism. Our findings indicate that the material is ceruloplasmin, that its rise correlates closely with plasma concentrations of PGE2-M, and that beth PGE2-M and ceruloplasmin increase in the plasma of tumor-bearing rabbits before the development of hypercalcemia.

Regulation of rabbit acute phase protein biosynthesis by monokines

“…Finally, our data have bearing on the role of prostaglandins in APP induction. Reports showing increased levels of Hp in rabbits [13,25] and CRP in man [26] following intravenous injection of PGE1 and PGE2 have raised the question of whether these PGEs act directly or indirectly upon hepatocytes. We have previously presented evidence that administration of prostaglandins does not influence CRP synthesis by rabbit hepatocytes [27].…”

“…Antibodies to rabbit albumin, Tf and a2M, all raised in the goat, and purified rabbit albumin and Tf were purchased from Cappel (Malvern, PA, U.S.A.). Goat anti-[human haptoglobin (Hp)] and ceruloplasmin (Cer), both of which cross-react with the corresponding rabbit proteins [13] and human standard serum-calibrator 1 were obtained from Atlantic Antibodies (Scarborough, ME, U.S.A.); sheep anti-(rabbit SAA) antibodies were a generous gift from Dr. J. B. Natvig (The National Hospital, Oslo, Norway).…”