Activated human PMN synthesize and release a strongly fucosylated glycoform of alpha1-acid glycoprotein, which is transiently deposited in human myocardial infarction.
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.
Poland
Dennis C W
DC
Department of Molecular Cell Biology & Immunology, VU University Medical Center, Van der Boechorststraat 7, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
García Vallejo
Juan-Jesús
JJ
Niessen
Hans W M
HW
Nijmeyer
Remco
R
Calafat
Jero
J
Hack
C Erik
CE
Van het Hof
Bert
B
Van Dijk
Willem
W
D003167:Complement Activation; D015926:Complement C3a / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005643:Fucose / Q000096:biosynthesis; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D009961:Orosomucoid / Q000096:biosynthesis*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational
D019040:E-Selectin; D009961:Orosomucoid; D005643:Fucose; D015926:Complement C3a