Platelet alpha granules contain a growth factor for fibroblasts

Abstract

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.

Agnogenic myeloid metaplasia (AMM)—correlation of bone marrow lesions with laboratory data: A longitudinal clinicopathological study on 114 patients

“…Pleomorphic appearance associated with abnormalities of maturation and bizarre and pyknotic forms (naked nuclei) were particularly conspicuous in megakaryocytes of patients with AMM (Buyssens and Bourgeois, 1977;Burkhardt et al, 1984Burkhardt et al, , 1986Georgii et al, 1984a,b;Frisch and Bartl, 1985;Wolf and Neiman, 1987). In vivo studies suggested an essential role of ineffective or defective megakaryopoiesis in fibrillogenesis by the release of mainly two factors: growth factor which stimulated fibroblast proliferation and collagen secretion and factor 4 which inhibited the activity of the enzyme collagenase (Kaplan et al, 1979;Castro-Malaspina et al, 198 1 ;Burstein et al, 1984;Castro-Malaspina, 1984).…”

Platelet‐derived growth factor‐B gene delivery sustains gingival fibroblast signal transduction

“…Two receptor isoforms with tyrosine kinase activity have been identified: platelet-derived growth factor-a receptor and platelet-derived growth factor-b receptor (1). Plateletderived growth factor binding to receptors activates a variety of intracellular signal molecules, such as phosphatidylinositol-3-kinase and Akt/ PKB, and subsequently exerts its biological effects on cell migration, proliferation, extracellular matrix synthesis and anti-apoptosis (2)(3)(4)(5)(6)(7).…”

Lysosomal Consept of Platelet Secretion ‐ Revisited

“…There is a distinct possibility, that during biochemical isolation procedures of platelet organelles, some of acid hydrolases may be lost as some are more easier and some less or nearly not at all solubilized, as was shown for platelet acid phosphatase, aryl sulfatase and suggested for betaglucuronidase (21,22,52). Thus some biochemical studies showed wide spread of lysosomal marker enzymes throughout the granule fractions (74)(75)(76)(77)(78)(79)(80), although some showed presence of only acid phosphatase activity in alphagranules (25). It was noted however, that alphagranules in the later study were somewhat swollen (79) and could have leaked other easier solubilized acid hydrolases while retaining acid phosphatase activity only.…”