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.
 ...
PMID:Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase. 754 38

Polyspecific and organ specific autoimmune diseases are often accompanied by prolonged clearance of immune complexes. In mice, impaired macrophage Fc gamma receptor function may be associated with autoantibody against Fc gamma receptors. To extend these observations to autoimmune human disease, we transformed with EBV peripheral lymphocytes from a patient with terminal progressive systemic sclerosis and screened for clones secreting anti-Fc gamma receptor Ig. A clone, N55, which secretes a high affinity anti-Fc gamma receptor IgG2 antibody was obtained. The Fab fragment of N55 bound to human neutrophils, NK cells, but not to monocytes, consistent with specificity for Fc gamma RIII (CD16). N55 Fab competed weakly for the binding of anti-Fc gamma RIII mAb 3G8 to neutrophils but did not have any effect on staining with the anti-Fc gamma RII mAb, IV.3. N55 Fab did not bind to peripheral monocytes, but did bind to monocytes incubated with TGF-beta (24 h) to induce Fc gamma RIII. The specificity of N55 IgG for Fc gamma RIII was confirmed by ELISA using secreted recombinant Fc gamma RIIA and Fc gamma RIIIB protein to coat microtiter wells. N55 IgG triggered the release from neutrophils of beta-glucuronidase, arylsulfatase and alkaline phosphatase. Such antibody may play a pathogenic role in progressive systemic sclerosis.
 ...
PMID:An Fc gamma RIII (CD16)-specific autoantibody from a patient with progressive systemic sclerosis. 838 99