Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD14 is a glycosylphosphatidylinositol (GPI)-anchored protein on the surfaces of monocytes and polymorphonuclear leukocytes (PMN) that binds and initiates cellular responses to bacterial LPS. PMN also contain an intracellular pool of CD14 that can be deployed rapidly to the cell surface in response to stimulation with a variety of agonists. To determine which of the well-characterized subcellular compartments of PMN contains CD14, cells were cavitated and fractionated on Percoll gradients. The gradient fractions were assayed for CD14 by ELISA and Western blot and for the marker proteins beta-glucuronidase (azurophil granules), vitamin B12 binding protein (specific granules), alkaline phosphatase (secretory vesicles and plasma membrane), and HLA (plasma membrane). Approximately one-half of the CD14 ran with plasma membrane fractions and one-half with intracellular membranes of light density. Both intracellular and cell surface CD14 were associated tightly with membrane, and both forms showed identical electrophoretic mobility. The intracellular CD14 was clearly not present in azurophil granules or specific granules, but ran precisely with alkaline phosphatase, a marker for secretory vesicles. Parallel studies showed that an additional GPI-linked protein, Fc gamma RIII (CD16), also fractionated precisely with CD14 and alkaline phosphatase. Association of CD14 with secretory vesicles were confirmed by studies on cells stimulated with the formyl peptide fNLLP for 20 min at 37 degrees C before fractionation. This treatment caused translocation of CD14 from intracellular fractions to plasma membrane fractions. No release of the specific granule marker vitamin B12 binding protein was observed under these conditions, whereas two other GPI-anchored proteins, alkaline phosphatase and CD16, moved coincidentally with CD14 to comigrate with the plasma membrane. Time course studies of CD14 and CD16 surface expression confirmed the rapid and coordinate up-regulation of these proteins. Thus, the intracellular compartment containing CD14 and CD16 had the properties of secretory vesicles. These vesicles may represent a specialized membrane domain of PMN enriched in GPI-anchored proteins.
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PMID:Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase. 754 38

Transendothelial migration of peripheral blood mononuclear cells (PBMCs) and their subsequent interaction with the subendothelial matrix lead to their differentiation to macrophages (mphis). To study whether preexposure of monocytes in circulation to modified proteins influences their differentiation to mphis, an in vitro model system using isolated PBMC in culture was used. The effect of modified proteins such as oxidatively modified LDL (ox-LDL), acetylated and non-enzymatically glycated-BSA (NEG-BSA) on the differentiation process was studied by monitoring the upregulation of mphi specific functions such as endocytosis, production of matrix metalloproteinases (MMPs), expression of surface antigen, activity of beta-glucuronidase and down regulation of monocyte specific myeloperoxidase activity. Rate of endocytosis, production of MMPs and beta-glucuronidase activity were significantly greater in cells treated with modified proteins irrespective of the nature of modification. Both CuSO4 ox-LDL and HOCl ox-LDL increased the rate of expression of the mphi specific functions. FACS analysis showed that the rate of upregulation of mphi specific CD71 and down regulation of monocyte specific CD14 were high in cells supplemented with modified proteins. Studies using PPARgamma antagonist and agonist suggest its involvement in CuSO4 ox-LDL induced monocyte-macrophage (mo-mphi) differentiation whereas the expression of macrophage specific functions in cells exposed to other modified proteins was independent of PPARgamma. PBMC isolated from hypercholesterolemic rabbits in culture expressed mphi specific functions at a faster rate compared to normal controls indicating that these observations are relevant in vivo. These results indicate that preexposure of monocytes to modified proteins promote their differentiation to mphis and may serve as a feed forward type control for clearing modified proteins.
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PMID:Influence of oxidatively modified LDL on monocyte-macrophage differentiation. 1766 Sep 56