Platelet-derived growth factor promotes polymorphonuclear leukocyte activation (original) (raw)
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Journal of Clinical Investigation, 1990
The chemotactic activities of three different isoforms of platelet-derived growth factor (PDGF) on fibroblasts, monocytes, and granulocytes of human origin were investigated. PDGF-AB and PDGF-BB induced strong, dose-dependent responses in both fibroblasts and monocytes, whereas PDGF-AA did not stimulate chemotaxis of these cell types. Instead, PDGF-AA inhibited the chemotactic activity of PDGF-AB and PDGF-BB on fibroblasts and monocytes. However, PDGF-AA was not able to block monocyte chemotaxis induced by FMLP. In contrast, in granulocytes, dose-dependent chemotactic responses were obtained with all three isoforms of PDGF. All isoforms gave maximal responses at concentrations between 5 and 20 ng/ml. At higher concentrations the migration was reduced. Reduction and alkylation of the PDGF molecule, which leads to loss of the mitogenic activity, also caused a loss of the chemotactic activities for all three cell types. The data suggest that the various isoforms of PDGF stimulate and inhibit chemotaxis in an isoformand cell type-specific manner.
The Journal of Cell Biology, 1985
Because platelet-derived growth factor (PDGF) may be released at sites where neutrophil proteinases may also be released, we examined the effects of neutrophil elastase and cathepsin G upon the chemotactic and mitogenic activities of PDGF. Elastase abolished the chemotactic activity of PDGF for fibroblasts but had no effect on its chemotactic activity for monocytes, or on its mitogenic activity for 3T3 cells or its capacity to bind to 3T3 cells. Cathepsin G had no effect upon the chemotactic or mitogenic activities of PDGF. In contrast, trypsin eliminated the chemotactic activity of PDGF for monocytes and fibroblasts and the mitogenic activity of PDGF. After reduction and alkylation, PDGF retained full chemotactic activity for fibroblasts and monocytes but exhibited no mitogenic activity and only limited binding to 3T3 cells. These results indicate separate domains on PDGF for fibroblast chemotactic and mitogenic activity and for monocyte and fibroblast chemotactic activity and rais...
Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor
Physiological Reviews, 1999
Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the α-receptor and the β-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involve...
The Journal of cell biology, 1983
The platelet-derived growth factor (PDGF) is the principal mitogen in serum for cultured cells of mesenchymal origin. PDGF also is a potent chemotactic protein for inflammatory cells and for cells required for wound repair. Because activity levels of PDGF in biological fluids are difficult to measure, we attempted to develop a radioimmunoassay for PDGF. Rabbits were immunized with purified PDGF; the antiserum obtained was monospecific for PDGF in immunodiffusion analysis against concentrated platelet lysates, serum, and plasma. A radioimmunoassay for PDGF was developed with a sensitivity of =0.2 ng/ml. Levels of PDGF in plasma/serum were measured and compared with PDGF levels determined by a receptor-competition assay and by a standard biological assay measuring incorporation of [3H]thymidine into 3T3 cells. Radioimmunoassay showed apparent PDGF levels of 50 ng/ml in human plasma and 103 ng/ml in serum. The 50 ng/ml PDGF in plasma was unexpected because the plasma samples contained little or no platelet release products as determined by very low levels of platelet factor 4. We therefore sought an immunologically reactive PDGF molecule in human plasma. No immunologically reactive protein was detected by immunodiffusion analysis or when plasma was treated with an immunoaffinity gel. Subsequently, a 1251-PDGF-binding protein was identified; the 1251-PDGF-plasma-binding protein complex was not reactive with anti-PDGF immunoglobulin. Correction for 1251-PDGF bound by the plasmabinding protein established serum levels of PDGF of-50 ng/ml; ~'50 ng/ml PDGF was found in serum by radioreceptor-competition assays and by mitogenic assays as well. The plasmabinding protein may serve to clear PDGF released in the circulation, thereby limiting PDGF activity to its local interactions at the site of blood-vessel injury. The platelet-derived growth factor (PDGF) ~ is a potent polypeptide growth factor released when platelets are activated during blood coagulation and at the site of blood-vessel injury. PDGF is strongly mitogenic for smooth muscle cells, skin fibroblasts, 3T3 cells, and cultured glial cells (1-9). PDGF recently was shown to have a second important biological activity in being a strong chemoattractant in vitro for human monocytes, neutrophils, fibroblasts, and for smooth muscles cells (10-13). While the precise roles of PDGF in vivo remain to be defined, these combined biological properties of PDGF as a potent mitogen and chemoattractant suggest a unique role for PDGF in inflammation and in wound healing. These properties also make PDGF an ideal agent to mediate several
Transfusion, 2010
BACKGROUND: Human platelet concentrates (PCs) may be a source material to produce purified growth factors (GFs) for clinical use or cell therapy. However, no fractionation process of therapeutic-grade GF from PCs has ever been developed. STUDY DESIGN AND METHODS: PCs were virally inactivated by solvent/detergent (S/D) treatment, subjected to oil extraction to remove part of the S/D agents, and fractionated on a SP-Sepharose (SP) chromatographic column equilibrated in a phosphatebuffered saline (PBS) buffer, pH 7.5. The breakthrough was recovered, and the column was washed with the PBS buffer and then eluted by a 0.7 mol/L NaCl-PBS buffer pH 7.5 (SP-eluate). The SP-breakthrough and SP-eluate were characterized for their content in GF, proteins, lipids, and S/D agents. The MTS value of three cell lines cultivated in a medium containing 10% fetal bovine serum supplemented with 1% to 3% of SP-eluate or recombinant human (rHu) platelet-derived growth factor (PDGF)-BB was compared. RESULTS: The SP-eluate contained a mean of 47, 17, and 6 ng/mL PDGF-AB,-BB, and-AA, respectively, and 0.26 ng/mL vascular endothelial growth factor (VEGF). It was largely depleted of transforming growth factor-b1 (2.33 ng/mL), epidermal growth factor (0.09 ng/mL), insulin-like growth factor (3.40 ng/mL), albumin, immunoglobulin (Ig)G, IgM, IgA, and fibrinogen, which were mostly in the breakthrough. tri-n-butyl phosphate and Triton X-45 were less than 2 ppm. Cell growthpromoting activity of the SP-eluate was at least as good as that of rHu-PDGF-BB. CONCLUSION: Human PC can be fractionated into a purified, virally inactivated PDGF and VEGF concentrate, opening perspectives for the development of a new range of blood products for clinical use and cell therapy procedures.
Synthesis of platelet-activating factor by human monocytes stimulated by platelet-activating factor
Journal of Allergy and Clinical Immunology, 1991
Increases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage after the late asthmatic response in an animal model. Am Rev Respir Dis 1985;131:875-9. 43. Lemanske R, Guthman D, Orgel H, Barr L, Kaliner M. The biological activity of mast cell granules. VI. The effect of vinblastine-induced neutropenia on rat cutaneous late-phase reactions. J Immunol 1983;130:2837-42. 44. Lemanske R, Guthman D, Kaliner M. The biologic activity of mast cell granules. VII. The effect of anti-neutrophil antibodyinduced neutropenia on rat cutaneous late-phase reactions.
In vitro effects of platelet factor 4 on normal human neutrophil functions
Journal of leukocyte biology, 1986
Platelet factor (PF4) prepared from human outdated platelets by heparinagarose affinity chromatography was confirmed to be chemotactic for human neutrophils and in a concentration-dependent fashion caused significant release of lysosomal enzymes (myeloperoxidase, lysozyme, beta-glucuronidase) from human neutrophils treated with cytochalasin B. Lysosomal enzyme release from PF4-stimulated neutrophils was rapid and reached a plateau by 1-3 min. PF4 did not cause release of the cytoplasmic enzyme lactate dehydrogenase which indicates that exocytosis of granule-containing lysosomal enzymes did not result from cytolysis. In contrast, superoxide anion generation from human neutrophils stimulated with PF4 was undetectable even at the highest PF4 concentration tested (2 X 10(-5) M). Pretreatment of neutrophils with PF4 caused significant increased adherence of neutrophils to plastic surfaces and cultured pulmonary artery endothelial cells. The concentration of PF4 that elicited neutrophil c...
Platelet alpha granules contain a growth factor for fibroblasts
Blood, 1979
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 a granules. The specific activity of platelet fibrinogen. an a-granule marker, was also highest in this fraction. The subcellular fractions were assayed for the presence of PDGF and for-thromboglobulin. PDGF was assayed quantitatively by the stimulation of DNA synthesis in confluent growtharrested BALB/c-3T3 cells, whereas the concentration of fl-thromboglobulin was determined by radioimmunoassay. The highest concentrations of both PDGF and ft-thromboglobulin were found in the a-granule fraction. In contrast,-glucuronidase, a lysosomal enzyme, was more diffusely distributed and had its highest specific activity in fractions of lower density than those for PDGF,-thromboglobulin, or fibrinogen. The data demonstrate that the a granules of platelets provide a unique delivery system for PDGF, a polypeptide hormone with growthpromoting activity for connective tissue cells. H UMAN PLATELETS contain a heat-stable (100#{176}C) polypeptide growth factor (PDGF) that is liberated into serum during the clotting process.'5 This polypeptide, which has recently been purified to homogeneity,6'7 stimulates the replication of fibroblasts,2'4ghial cells,3 and smooth-muscle cells in vitro.' It is not required to sustain the growth of virus-transformed fibroblasts.8 Platelets provide storage and a transport system for PDGF and other polypeptides, including f3-thromboghobuhin,9" platelet factor 4,''' and fibrinogen.'6 These polypeptides, as well as serotonin, lysosomal enzymes, and other substances, are released during the clotting Fibrinogen and platelet factor 4 are
FEBS Letters, 1989
Additon of opsonized particles to human neutrophils in suspension leads to a biphasic elevation in the cytosolic free Ca2+ concentration ([Ca*'],). The rise in [Caz'], during the second phase (> 3 min) is pronounced (about 400 nM), in contrast to the rise during the first phase, which is relatively small (< 100 nM). The second and large rise in [Ca"], is brought about by messenger(s) released from the cell after addition of opsonized particles. This second rise in [Ca*+], is not observed in the presence. of the platelet-activating factor (PAF) antagonist WEB 2086, indicating that PAF can act as an intercellular messenger affecting Ca 2+ homeostasis in human neutrophils.