Effect of Acute Phase Protein, Alpha – 1 – Acid Glycoprotein (AGP-1), On Platelet-Activating Factor (PAF) – Induced Pro-Inflammatory Responses

Life Science - Biochemistry

Abstract

Alpha-1-acid glycoprotein (AGP-1), an acute phase protein with ill defined functions, circulates in blood (sAGP-1) at basal levels, but levels can go up several fold upon inflammatory stimuli. Very recently, AGP-1 is shown to play a critical role in the inflammatory process by interacting with inflammatory molecules and/ or cells of the immune system. However, the interactions of sAGP-1 with endogenous inflammatory lipid mediators like Platelet-activating factor (PAF) are not well characterized. PAF is a potent autocoid with implications in several inflammatory disorders and is known to activate various cells of the innate immune system. To address this issue, we looked into the effect of sAGP-1 in PAF-induced sudden death models using Swiss Wistar (albino) mice established previously in our laboratory, to find sAGP-1 neither augmented nor inhibited the lethality of PAF in vivo. To dissect the mechanism behind this, we employed primary immune cell type namely, human neutrophils. We found that both sAGP-1 and PAF are potent activators of neutrophil adhesion and in fact, sAGP-1 even augmented PAF-induced neutrophil adhesion. Although sAGP-1 is a potent activator of neutrophils, for some responses such as PAF-induced NETosis, sAGP-1 was without any effect. These results shed light on the pro-inflammatory actions of sAGP-1 and its implications in some of the hyper-inflammatory disorders where involvement of PAF is also suspected.