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The acute phase response of plasma protein synthesis during experimental inflammation.

1982; Elsevier BV; Volume: 257; Issue: 17 Linguagem: Inglês

10.1016/s0021-9258(18)34015-8

1083-351X

Gerhard Schreiber, G.J. Howlett, Mariko Nagashima, Anne Millership, Harry Martin, J. Urban, Leore Kotler,

Iron Metabolism and Disorders

The effect of acute inflammation on the synthesis of plasma proteins by the liver was studied in rats.The rates of incorporation of ~-[I-'~C]leucine into proteins in the bloodstream changed 24 h after injection of turpentine by the following factors: total serum protein, 1.6; al-acid glycoprotein and major acute phase al-protein, 20; fibrinogen, 4.8; transferrin, 1.3; albumin, 0.4.The changes in incorporation rates preceded changes in concentrations of the above proteins in plasma.The total body pools, measured in whole rat homogenates 3 days after inducing inflammation, increased 18-fold for major acute phase a,-protein, 14-fold for al- acid glycoprotein, and decreased for albumin to 0.66 of the value in healthy rats.The total body pool of transferrin remained constant for about 24 h and increased slightly after 3 days to a value about 1.3 times larger than that in healthy rats.The rate of degradation of transferrin was not influenced by inflammation.The rates of synthesis of specific plasma proteins in healthy rats (steady state) were determined from the total body pools and the turnover of injected 1251-labeled proteins.The proportions of the rates of synthesis were the same as those of the rates of incorporation, after correcting for differences in leucine content, suggesting that these proteins were synthesized from the same intracellular leucine pools.Using the constant rate of synthesis of transferrin as a reference, the following changes in net synthesis rates, 24 h after inducing inflammation, were calculated: albumin, 91 to 32; major acute phase a,-protein, 2.3 to 64, al-acid glycoprotein, 1.0 to 22 mg/lOO g of body weight/day.The synthesis of serum total protein increased from 234 to 380 mg/100 g of body weightjday after inflammation for 24 h.Distinct and coordinated changes in the concentration of individual proteins in the plasma can be observed during acute inflammation (for review see Ref. 1).Increased rates of incorporation of radioactive amino acids into proteins in the plasma during inflammation, such as those described for the major acute phase aI-protein of the rat (2) and for cul-acid glycoprotein in in vitro studies with liver slices (3) or hepatocytes in culture (4) suggest that, at least in part, the increase in the plasma concentration of the acute phase reactants during inflammation is due to increased rates of synthesis.In the following, the acute phase response of the protein-