Activated human PMN synthesize and release a strongly fucosylated glycoform of α1-acid glycoprotein, which is transiently deposited in human myocardial infarction

Abstract

␣ 1 -Acid glycoprotein (AGP) is a major acute-phase protein present in human plasma as well as in polymorphonuclear leukocytes (PMN). In this report, we show that PMN synthesize a specific glycoform of AGP, which is stored in the specific and azurophilic granules. Activation of PMN results in the rapid release of soluble AGP. PMN AGP exhibits a substantially higher apparent molecular weight than plasma AGP (50 -60 kD vs. 40 -43 kD), owing to the presence of strongly fucosylated and sialylated polylactosamine units on its five Nlinked glycans. PMN AGP is also released in vivo from activated PMN, as appeared from studies using well-characterized myocard slices of patients that had died within 2 weeks after an acute myocardial infarction. AGP was found deposited transiently on damaged cardiomyocytes in areas with infiltrating PMN only. It is interesting that this was inversely related to the deposition of activated complement C3. Strongly fucosylated and sialylated AGP glycoforms have the ability to bind to E-selectin and to inhibit complement activation. We suggest that AGP glycoforms in PMN provide an endogenous feedback-inhibitory response to excessive inflammation. J. Leukoc. Biol. 78: 453-461; 2005.

Acute phase proteins in ruminants

“…These concentrations can hardly be achieved in serum, even after an acute phase reaction, but it is possible that due to the local expression [33,95], or its transport to the inflamed tissues via the granulocytes [96][97][98], the concentration of AGP in the inflammatory focus is raised to very high levels.…”

The Acute Phase Protein α1-Acid Glycoprotein: A Model for Altered Glycosylation During Diseases

“…Human granulocytes synthesize a specific glycoform of AGP, which is stored in the specific azurophylic granules, and is rapidly released together with lactoferrin following activation. AGP's expression in a myeloid cell line can be induced by members of the C/EBP (CCAAT/enhancer-binding protein) family [26,27]. Finally, high levels of mRNA coding for AGP were detected during early fetal development in rat placenta [28]: in situ hybridization histochemistry revealed that AGP mRNA was expressed in a subpopulation of deciduals cells found in decidua capsularis, and later, in decidua basalis [29].…”

Statistical evaluation of CZE‐UV and CZE‐ESI‐MS data of intact α‐1‐acid glycoprotein isoforms for their use as potential biomarkers in bladder cancer

“…Serum concentration of AGP in healthy individuals is about 0.4-0.7 mg/mL and an increase in its blood level has been related to cancer [3][4][5][6]. However, an increase of total AGP level can be also related to acute phase reactions as well as to other pathologies, such as cardiovascular diseases [7,8]. For this reason, a more specific characteristic of this protein has to be investigated for its relation with cancer.…”