Alpha dependent manner, although concentrations needed toAlpha dependent manner, although concentrations needed to

Alpha acid glycoprotein-1(AGP-1) also refered as Orosomucoid, is a major acute phase protein of hepatic origin in humans, mice and rats, whose levels elevate several folds in plasma upon an inflammatory insult (infection, pregnancy, sepsis) (). Despite AGP-1’s potent yet enigmatic cytoprotective and anti-inflammatory responses in vivo and vitro (), its biological function is still obscure. The plasma concentration of AGP-1 in different species during normal conditions and extent of increase in levels during acute phase reaction are mentioned in the table below.Human AGP-1 is an extensively glycosylated protein with glycopart accounting for ~45% of its 43 kDa molecular weight() with 3-5 highly sialylated carbohydrate side chains. Altered glycosylation pattern has been attributed to severity of the diseases and AGP-1 functions. The protein part of AGP-1 is a product of cluster of three adjacent genes: AGP-A, AGP-B and AGP-B  covering 70kb of the human genome, located on chromosome 9. Only AGP-A can be induced by acute-phase stimuli and is regulated by IL-1, IL-6 and glucocorticoids (). The AGP-A gene product is single polypeptide of 183 amino acid residues.The biological function of AGP-1 is still enigmatic.  It has been suggested to bind various drugs.  It is known to exert antiproliferative action on phytohemaglutinin (PHA) and LPS stimulated proliferation of peripheral T-lymphocytes(). In vitro, it also inhibits the growth of cancer cells at high concentration(). During inflammation, neutrophils are the first cell types to be recruited to the site of infection or injury. AGP-1 has been suggested to inhibit several activities of neutrophils ()-thus mediating an anti-inflammatory response.  AGP-1 also suppresses carrageen and dextran induced rat paw edema(). AGP-1 has  been shown to inhibit platelet aggregation induced by ADP, epinephrine and thrombin in a dose dependent manner, although concentrations needed to achieve this was  high (1.25-7.5mg/ml), and our preliminary data suggest this may not be the case. AGP-1 also seems to protect mice from TNF-? induced lethal shock() but not against  LPS  induced shock (). Fig (1)   provides an overview of various effects of AGP-1 among different vascular cells. Various drugs bind to AGP-1, although this property is not evolutionarily selected trait. Even though an immune modulatory function of AGP is described, a clear cut physiological function is not ascribed yet. In some instances it appears to act like anti-inflammatory protein, while in other situations it appears to be pro-inflammatory. Secondly pattern of glycosylation influences the AGP activities.  Further, its actions are cell type and stimulus dependent.  Moreover, some activities are concentration dependent as well.