Increased sialylation and defucosylation of plasma proteins are early events in the acute phase response

Abstract

Within hours of turpentine injection to stimulate the acute phase (AP) response in rats, the N-acetylneuraminic acid content of plasma proteins increases and that of fucose decreases, each by about 60%. The two changes are inversely related (r = -0.97). The NeuAc/Gal ratio increases from the normal 0.75 to 1.0 on day 2 of the AP. Whereas 50% of the isolated oligosaccharides of normal plasma proteins are retarded on immobilized Ricinus communis agglutinin, those from day 2 AP plasma fail to do so. This indicates that NeuAc caps the normally Gal-terminated chains. alpha1-Acid glycoprotein (a positive AP protein), alpha1-macroglobulin (a non-AP protein), and alpha1-inhibitor3 (a negative AP protein) also show similar alterations in NeuAc/Gal ratio and decreases in Fuc. alpha2-Macroglobulin, which arises only during the AP, does not contain significant amounts of Fuc. Sambucus nigra agglutinin (alpha2,6-linked NeuAc-specific) binds a majority of plasma proteins, and binding is increased during the AP response. Maackia amurensis lectin (alpha2,3-linked NeuAc-specific) binds only three proteins in normal plasma and three additional proteins in AP plasma. The Fuc-specific Aleuria aurantia agglutinin and Lens culinaris agglutinin each detect five proteins in normal plasma. Their binding decreases during the AP response. These results show that: (1) sialylation and defucosylation of preexisting plasma proteins occur rapidly in the AP response; (2) sialylation caps the preexisting Gal-terminating oligosaccharides; and (3) the oligosaccharides of even the non-AP and negative AP proteins are modified. These changes are distinct from the elevation in the levels of protein-bound monosaccharides and the altered concanavalin A-binding profile the oligosaccharides of AP proteins acquire in diseases.

Alteration of the Serum N-glycome of Mice Locally Exposed to High Doses of Ionizing Radiation

“…These changes might explain the observed shifts of spot trains toward acidic pH levels in two-dimensional DIGE in our previous work (16) and for both mouse and human serum proteins in this study. In accordance with our results, a total increase in sialylation has been observed when an acute phase response was induced in mice via turpentine oil injection (27,43). Moreover, increased sialylation was related to the production of the proinflammatory cytokine IL-6 in patients with cystic fibrosis (44) and in patients with gastric cancer (45).…”

Effect of Bu-Zhong-Yi-Qi-Tang on deficiency of N-glycan/nitric oxide and islet damage induced by streptozotocin indiabetic rats

“…PNA is a lectin with a high binding affinity for galactosegalactosamine disaccharide [21] . NeuAc caps the galactoseterminated chains [22] . Like ConA, LCA is able to bind (or not bind) to the same glycopeptides.…”

Liver Membrane Proteome Glycosylation Changes in Mice Bearing an Extra-hepatic Tumor

“…These sialyltransferases are mostly involved in the addition of ␣ (2,3) and ␣ (2,6) sialic acids onto N-and O-glycans. Most plasma proteins are derived from the liver and significant increases in serum acute phase glycoproteins and their sialylation have generally been observed with most rodent experimental inflammation models (31)(32)(33).…”