Linked Life Data

1698792

Source:http://linkedlifedata.com/resource/pubmed/id/1698792

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-11-21
pubmed:abstractText
alpha-Macroglobulins derived from plasma or secreted by macrophages are platelet-derived growth factor (PDGF) binding proteins that compete with cell-surface receptors on fibroblasts for PDGF binding. alpha 2-Macroglobulin (alpha 2M) derived from bovine plasma was tested for its ability to modulate the PDGF-induced proliferation of primary passage rat lung fibroblasts (RLFs) and a human skin fibroblast cell line (CRL 1508). Fibroblasts were grown in 10% fetal bovine serum (FBS) for 24 hr, then washed with serum-free medium before adding serum-free defined medium (SFDM) containing insulin and transferrin. To this medium were added varying concentrations of human plasma-derived AB-PDGF and alpha 2 M, alone or in combination. Receptor-recognized alpha 2M was prepared by treatment with methylamine. Both native alpha 2M and the alpha 2M-methylamine (alpha 2M-MA) were tested for growth promoting activity in the absence or presence of PDGF. After 3 days, a concentration-dependent growth curve of fibroblast proliferation was demonstrated for PDGF alone, with near maximal stimulation reached at 15-20 ng/ml PDGF. alpha 2M and alpha 2M-MA alone had no effect on cell proliferation. However, alpha 2M-MA concentrations above 32 micrograms/ml synergistically enhanced PDGF-stimulated proliferation greater than 100% in the presence of 15 ng/ml PDGF. Native alpha 2M enhanced PDGF-stimulated growth 80-100% above PDGF controls only at low concentrations (32-64 micrograms/ml alpha 2M). High concentrations of native alpha 2M (128-256 micrograms/ml) either had no effect on growth or were inhibitory to PDGF-stimulated growth, depending on the cell type tested. Rat lung fibroblasts were shown to secrete a factor(s) that inhibited the trypsin-binding capacity of native alpha 2M. We further demonstrated that early passage RLFs possess specific cell-surface receptors for [125I]-PDGF and [125I]-alpha 2M-MA, and preincubation of RLFs with alpha 2M-MA increased the specific binding of [125I]-PDGF to the cell surface of these fibroblasts. Considered together, these data support the view that receptor-recognized alpha 2M synergistically enhances the proliferative capacity of PDGF. We postulate that receptor-recognized alpha Ms enhance PDGF-stimulated growth by increasing the local concentration of PDGF at the cell surface, where the PDGF could be released in close proximity to its own receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
145
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-8
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:1698792-Animals, pubmed-meshheading:1698792-Binding, Competitive, pubmed-meshheading:1698792-Cell Division, pubmed-meshheading:1698792-Fibroblasts, pubmed-meshheading:1698792-Humans, pubmed-meshheading:1698792-Iodine Radioisotopes, pubmed-meshheading:1698792-Kinetics, pubmed-meshheading:1698792-Low Density Lipoprotein Receptor-Related Protein-1, pubmed-meshheading:1698792-Lung, pubmed-meshheading:1698792-Methylamines, pubmed-meshheading:1698792-Platelet-Derived Growth Factor, pubmed-meshheading:1698792-Radioligand Assay, pubmed-meshheading:1698792-Rats, pubmed-meshheading:1698792-Receptors, Cell Surface, pubmed-meshheading:1698792-Receptors, Immunologic, pubmed-meshheading:1698792-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:1698792-Skin, pubmed-meshheading:1698792-alpha-Macroglobulins
pubmed:year
1990
pubmed:articleTitle
PDGF-stimulated fibroblast proliferation is enhanced synergistically by receptor-recognized alpha 2-macroglobulin.
pubmed:affiliation
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
pubmed:publicationType
Journal Article, In Vitro