Activated human PMN synthesize and release a strongly fucosylated glycoform of alpha1-acid glycoprotein, which is transiently deposited in human myocardial infarction

Dennis C W Poland, Juan-Jesús García Vallejo, Hans W M Niessen, Remco Nijmeyer, Jero Calafat, C Erik Hack, Bert Van het Hof, Willem Van Dijk

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Alpha1-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 N-linked 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.

Original languageEnglish
Pages (from-to)453-61
Number of pages9
JournalJournal of Leukocyte Biology
Volume78
Issue number2
DOIs
Publication statusPublished - Aug 2005

Cite this

@article{ac641c5cd72946f09674e02b18f80aad,
title = "Activated human PMN synthesize and release a strongly fucosylated glycoform of alpha1-acid glycoprotein, which is transiently deposited in human myocardial infarction",
abstract = "Alpha1-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 N-linked 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.",
keywords = "Complement Activation, Complement C3a, Cytoplasmic Granules, E-Selectin, Female, Fucose, Glycosylation, Humans, Inflammation, Male, Myocardial Infarction, Myocardium, Myocytes, Cardiac, Neutrophils, Orosomucoid, Protein Binding, Protein Processing, Post-Translational, Journal Article, Research Support, Non-U.S. Gov't",
author = "Poland, {Dennis C W} and {Garc{\'i}a Vallejo}, Juan-Jes{\'u}s and Niessen, {Hans W M} and Remco Nijmeyer and Jero Calafat and Hack, {C Erik} and {Van het Hof}, Bert and {Van Dijk}, Willem",
year = "2005",
month = "8",
doi = "10.1189/jlb.1004566",
language = "English",
volume = "78",
pages = "453--61",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "2",

}

Activated human PMN synthesize and release a strongly fucosylated glycoform of alpha1-acid glycoprotein, which is transiently deposited in human myocardial infarction. / Poland, Dennis C W; García Vallejo, Juan-Jesús; Niessen, Hans W M; Nijmeyer, Remco; Calafat, Jero; Hack, C Erik; Van het Hof, Bert; Van Dijk, Willem.

In: Journal of Leukocyte Biology, Vol. 78, No. 2, 08.2005, p. 453-61.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Activated human PMN synthesize and release a strongly fucosylated glycoform of alpha1-acid glycoprotein, which is transiently deposited in human myocardial infarction

AU - Poland, Dennis C W

AU - García Vallejo, Juan-Jesús

AU - Niessen, Hans W M

AU - Nijmeyer, Remco

AU - Calafat, Jero

AU - Hack, C Erik

AU - Van het Hof, Bert

AU - Van Dijk, Willem

PY - 2005/8

Y1 - 2005/8

N2 - Alpha1-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 N-linked 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.

AB - Alpha1-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 N-linked 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.

KW - Complement Activation

KW - Complement C3a

KW - Cytoplasmic Granules

KW - E-Selectin

KW - Female

KW - Fucose

KW - Glycosylation

KW - Humans

KW - Inflammation

KW - Male

KW - Myocardial Infarction

KW - Myocardium

KW - Myocytes, Cardiac

KW - Neutrophils

KW - Orosomucoid

KW - Protein Binding

KW - Protein Processing, Post-Translational

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1189/jlb.1004566

DO - 10.1189/jlb.1004566

M3 - Article

VL - 78

SP - 453

EP - 461

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 2

ER -