Highly glycosylated α1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils

摘要: Alpha-1-acid glycoprotein (AGP) is an acute-phase protein produced by hepatocytes and secreted into plasma in response to infection/injury. We recently assessed the transcriptional program of terminal granulocytic differentiation microarray analysis bone marrow (BM) populations highly enriched promyelocytes, myelocytes/metamyelocytes (MYs), BM neutrophils. These analyses demonstrated a transient, high mRNA expression genuine secondary/tertiary granule proteins AGP MYs. In agreement with this, immunocytochemistry revealed presence secondary lactoferrin cells from MY stage throughout differentiation. Immunoelectron microscopy colocalization granules This finding was substantiated failure detect blood patient (specific) deficiency. addition, Western blot subcellular fractions isolated neutrophils that neutrophil-derived AGP, localized granules, abundant glycosylated compared endocytosed, plasma-derived secretory vesicles. Exocytosis studies further marked release activated Finally, induction CCAAT/enhancer-binding (C/EBP)-epsilon myeloid cell line shown increase transcript levels, indicating cells, like hepatocytes, partially regulated members C/EBP family. Overall, these findings define as Hence, neutrophils, which constitute first defense, are likely serve primary local source at sites infection or injury.