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

Platelets contain a polypeptide growth factor that stimulates the replication of normal connective tissue cells; this platelet-derived growth factor (PDGF) is released during the clotting process. Human platelets from normal volunteers were disrupted by nitrogen cavitation, and the subcellular organelles were fractionated by ultracentrifugation through a 30%--60% sucrose gradient. Electron microscopy revealed that fraction 7 (density 1.23 g/liter) contained the largest number of alpha granules. The specific activity of platelet fibrinogen, an alpha-granule marker, was also highest in this fraction. The subcellular fractions were assay for the presence of PDGF and for beta-thromboglobulin. PDGF was assayed quantitatively by the stimulation of DNA synthesis in confluent growth-arrested BALB/c-3T3 cells, whereas the concentration of beta-thromboglobulin was determined by radioimmunoassay. The highest concentrations of both PDGF and beta-thromboglobulin were found in the alpha-granule fraction. In contrast, beta-glucuronidase, a lysosomal enzyme, was more diffusely distributed and had its highest specific activity in fractions of lower density than those for PDGS, beta-thromboglobulin, or fibrinogen. The data demonstrate that the alpha granules of platelets provide a unique delivery system for PDGF, a polypeptide hormone with growth-promoting activity for connective tissue cells.
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PMID:Platelet alpha granules contain a growth factor for fibroblasts. 44 48

During in vitro culture arterial smooth muscle cells of adult rats are able to produce a platelet-derived growth factor (PDGF)-like protein and to promote their own growth in an autocrine manner. Here, this process has been studied using suramin, a polyanionic drug that has been reported to interfere with the cellular binding of several growth factors. Our results indicate that suramin speeds up the transition of the cells from a contractile to a synthetic phenotype early in primary culture. It inhibits the binding of PDGF to the cells, displaces PDGF bound to the cell surface, and slows down the degradation of PDGF internalized by the cells. It reduces the specific activities of the lysosomal enzymes acid phosphatase, beta-N-acetylglucosaminidase and beta-glucuronidase, and gives rise to an accumulation of lysosomes with myelin-like inclusions. It blocks PDGF- and serum-induced DNA synthesis and cellular proliferation in secondary cultures, but lacks a distinct inhibitory effect on DNA synthesis in primary cultures under serum-free conditions. The results suggest that the PDGF-like protein produced by the smooth muscle cells under the latter conditions may bind to its receptor and exert its autocrine effect intracellularly, without prior release into the pericellular space.
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PMID:Suramin inhibits binding and degradation of platelet-derived growth factor in arterial smooth muscle cells but does not interfere with autocrine stimulation of DNA synthesis. 271 95

Like in the polymorphonuclear leukocyte (PMN), the platelet-derived growth factor (PDGF) purified to homogeneity is capable of inducing monocyte activation responses as evaluated by generation of superoxide anion (O-.2) from membrane-associated oxidase system, release of granule enzymes, and enhanced cell adherence and cell aggregation. Superoxide anion release was maximized at 10 ng/mL PDGF and was comparable to that induced by 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine. The potency of PDGF to induce this response in monocytes was of the same magnitude as that observed in PMNs. Similarly, lysozyme release and monocyte adherence were also increased in a dose-dependent manner and achieved maximal responses at 40 ng/mL concentration of PDGF. The PDGF concentration required to achieve maximal monocyte aggregation was two-fold (60 ng/mL) of that found for PMNs. In contrast to PMNs, a positive correlation (gamma = .93; P less than .01) was observed between the increases of PDGF concentration and beta-glucuronidase release. These findings indicate that PDGF can induce the full sequence of cell activation events in human monocytes similar to human PMNs.
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PMID:Platelet-derived growth factor promotes human peripheral monocyte activation. 298 67

Fibrin formation and turnover are intimately associated with inflammation and wound healing. To explore whether fibrin(ogen)-derived peptides exert direct effects upon cells involved in inflammation and tissue repair we examined the capacity of human fibrinopeptide B (hFpB), a thrombin-derived proteolytic cleavage product of the fibrinogen B beta-chain, to stimulate neutrophils (PMN), monocytes, and fibroblasts. hFpB caused directed cell migration of PMN and fibroblasts that was optimal at approximately 10(-8) M. This chemotactic activity was blocked by preincubating hFpB with antiserum to hFpB. hFpB was not chemotactic for monocytes. The chemotactic potency of hFpB for PMN was equivalent to that of anaphylatoxin from the fifth component of human complement (C5a), leukotriene B4 (LTB4), and formyl-methionyl-leucyl-phenylalanine (fMLP), and for fibroblasts its chemotactic activity was comparable to that of platelet-derived growth factor. hFpB did not interact with PMN receptors for C5a, LTB4, or fMLP as (a) desensitization with 10(-7) M hFpB abolished chemotaxis to hFpB but had no effect upon chemotaxis to C5a, LTB4, or fMLP and (b) induction of chemotactic responses to fMLP and LTB4 in neutrophilic leukemic cells (HL-60 cells) by incubation with dimethylsulfoxide did not extend to hFpB. Like fMLP, hFpB caused a rapid, dose-dependent increase in PMN cytoskeletal associated actin, but unlike fMLP, hFpB did not cause PMN aggregation, release of lysosomal enzymes (lysozyme and beta-glucuronidase), or the production of superoxide anion. These results suggest that hFpB may have a role in recruiting PMN and fibroblasts at sites of fibrin deposition and turnover. The capacity of hFpB to cause PMN chemotaxis without causing concurrent release of lysosomal enzymes or the production of superoxide anion is further evidence for the complexity of PMN responses to chemotactic agents.
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PMID:Effects of fibrinogen derivatives upon the inflammatory response. Studies with human fibrinopeptide B. 300 61

The objective of this study was to investigate the mechanisms that contribute to the generation of macrophage functional diversity. Exposure of mouse bone marrow-derived macrophages to beta-1,3-glucan, a particulate inflammatory stimulus, or polyinosinate-polycytidylate (poly[I:C]), a stimulus of macrophage cytocidal activation, induced distinct and stimulus-specific patterns of gene expression. These changes were characterized by an up-regulation of the expression of the acid hydrolase beta-glucuronidase and platelet-derived growth factor B following incubation with beta-1,3-glucan and a stimulation of the expression of the complement component Bf, beta-interferon, and the reactive nitrogen intermediates NO2/NO3 during incubation with poly[I:C]. The induction of Bf expression by poly[I:C] could not be explained on the basis of distinct subpopulations of cells since in situ hybridization with a mouse Bf cRNA probe revealed a uniform and substantial increase in Bf expression by the entire population of cells. Incubation of macrophages with beta-1,3-glucan before stimulation with poly[I:C] was found to strongly attenuate the expression of Bf and beta-interferon. Conversely, incubation with poly[I:C] prior to exposure to beta-1,3-glucan substantially blocked the stimulation of beta-glucuronidase and platelet-derived growth factor B expression, indicating that these two responses were expressed in a mutually antagonistic fashion. However, after removal of either stimulus and following a period in which the primary response was allowed to decay, the cells regained their capacity to subsequently respond to either the same stimulus or to a different stimulus. Collectively, these findings indicate, first, that the heterogeneity of gene expression seen in response to poly[I:C] represents an adaptive response of the entire macrophage population rather than the restricted responses of distinct subpopulations of cells. Second, macrophages respond to these stimuli in a sequential fashion. These findings thus have a significant bearing on our understanding of the regulation of macrophage heterogeneity in host defense.
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PMID:Development of functional diversity in mouse macrophages. Mutual exclusion of two phenotypic states. 834 4