| Autor: |
Sumanth, Mosale Seetharam, Jacob, Shancy P., Abhilasha, Kandahalli Venkataranganayaka, Manne, Bhanu Kanth, Basrur, Venkatesha, Lehoux, Sylvain, Campbell, Robert A., Yost, Christian C., McIntyre, Thomas M., Cummings, Richard D., Weyrich, Andrew S., Rondina, Matthew T., Marathe, Gopal K |
| Předmět: |
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| Zdroj: |
Journal of Leukocyte Biology; May2021, Vol. 109 Issue 5, p915-930, 16p |
| Abstrakt: |
Alpha‐1‐acid glycoprotein (AGP‐1) is a positive acute phase glycoprotein with uncertain functions. Serum AGP‐1 (sAGP‐1) is primarily derived from hepatocytes and circulates as 12–20 different glycoforms. We isolated a glycoform secreted from platelet‐activating factor (PAF)‐stimulated human neutrophils (nAGP‐1). Its peptide sequence was identical to hepatocyte‐derived sAGP‐1, but nAGP‐1 differed from sAGP‐1 in its chromatographic behavior, electrophoretic mobility, and pattern of glycosylation. The function of these 2 glycoforms also differed. sAGP‐1 activated neutrophil adhesion, migration, and neutrophil extracellular traps (NETosis) involving myeloperoxidase, peptidylarginine deiminase 4, and phosphorylation of ERK in a dose‐dependent fashion, whereas nAGP‐1 was ineffective as an agonist for these events. Furthermore, sAGP‐1, but not nAGP‐1, inhibited LPS‐stimulated NETosis. Interestingly, nAGP‐1 inhibited sAGP‐1‐stimulated neutrophil NETosis. The discordant effect of the differentially glycosylated AGP‐1 glycoforms was also observed in platelets where neither of the AGP‐1 glycoforms alone stimulated aggregation of washed human platelets, but sAGP‐1, and not nAGP‐1, inhibited aggregation induced by PAF or ADP, but not by thrombin. These functional effects of sAGP‐1 correlated with intracellular cAMP accumulation and phosphorylation of the protein kinase A substrate vasodilator‐stimulated phosphoprotein and reduction of Akt, ERK, and p38 phosphorylation. Thus, the sAGP‐1 glycoform limits platelet reactivity, whereas nAGP‐1 glycoform also limits proinflammatory actions of sAGP‐1. These studies identify new functions for this acute phase glycoprotein and demonstrate that the glycosylation of AGP‐1 controls its effects on 2 critical cells of acute inflammation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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