Pig α1-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein

Abstract

The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1–3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2–5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein.

Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation‐associated protein HP‐27

“…α1AG is in most species a positive acute phase protein, but data on pig are slightly controversial, probably breed‐dependent. Recent evidences suggest that α1AG is a negative acute phase protein in the pig during infection , whereas it has been observed that obese pigs from certain breeds show significantly higher serum levels of α1AG compared to lean counterparts . In humans, the levels of serum α1AG rise with obesity, which is considered as a sign of overweight‐associated low‐grade inflammation .…”

“…In humans, the levels of serum α1AG rise with obesity, which is considered as a sign of overweight‐associated low‐grade inflammation . Interestingly, levels of this protein have also been identified to be strongly inversely correlated with growth rate in swine in different studies, in the absence of confounding environmental, health and management factors . It is therefore possible that different genetic backgrounds and inflammatory stimuli result in different responses of α1AG.…”

Pharmacokinetic and Pharmacodynamic Considerations for Drugs Binding to Alpha-1-Acid Glycoprotein

“…There is little characterization of monkey AAG in the literature, though it has also been reported to be lower in cynomolgus monkey (0.1 mg/ml) compared to human (30). The conventional pig is the only species where AAG levels have been reported to be higher (1.1-2.5 mg/ml) (14,18) compared to human. However, this finding has not been consistently observed, lower AAG values of 0.24 mg/ml (16) and 0.34 mg/ml (15) have also been reported in the conventional pig.…”

α 1-acid glycoprotein inhibits lipogenesis in neonatal swine adipose tissue

“…(Boncela et al, 2001); however, in that study AGP did not interfere with PAI-1 activity. As previously mentioned, serum AGP concentrations increase during late gestation in the pig and are highest at birth (Lampreave and Piñeiro, 1992), then rapidly decline postnatally Heegaard et al, 2013). The interaction of AGP with insulin to reduce insulin-mediated lipogenesis may be especially important in the fetal pig during late gestation when lipid accumulation within adipose tissue is restricted due to the relative unavailability of exogenous lipids and the consequent reliance on glucose for de novo lipogenesis in the fetus (Mersmann, 1974).…”