Systemic
injuries provoke a coordinate change in the hepatic synthesis and circulating concentration of
plasma proteins. To assess the effect of a transition from acute to chronic
inflammation on the expression of the
plasma protein genes, the qualitative and quantitative changes of liver
mRNA were measured in males of the inbred strain C57BL/6 of Mus musculus during a 14-day period of
inflammation.
Inflammation was induced and maintained by repeated
injections of the irritants,
turpentine,
lipopolysaccharides, and
celite. At various times, total
RNA was extracted from the liver. The concentration of specific
mRNA was quantitated by cellfree translation and by blot hybridization with
cDNA. The
mRNA for the increased
plasma proteins serum amyloid A,
alpha 1-acid glycoprotein,
haptoglobin, and alpha-
fibrinogen showed essentially the same time course of changes. The concentrations were maximal 24 hr after initiation of
inflammation and then declined gradually during the following days. During the progression from acute to chronic
inflammation, there was a switch from a predominant expression of the gene for alpha 1-acid glycoprotein-1 to one of alpha 1-acid glycoprotein-2. The prolonged
inflammation had an inverse effect on the two major negative
acute-phase reactants,
albumin and
major urinary proteins. The concentration of
albumin mRNA was reduced to 50% after 24 hr of
inflammation but returned to the control level within 5 days. The
mRNA for
major urinary proteins, however, were lowered within 2 to 5 days of
inflammation to 10 to 20% and were maintained at that level. These results suggest that different regulatory factors, humoral and/or cellular, are involved in controlling the expression of the genes for positive and negative acute-phase
plasma proteins during acute and chronic
inflammation.