Document Detail


Polymorphonuclear leukocytes enhance release of growth factors by cultured endothelial cells.
MedLine Citation:
PMID:  8274467     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Porcine aortic endothelial cells (PAECs) in culture constitutively secrete polypeptide (endothelium-derived) growth factors (EDGFs) into the surrounding medium. Incubation of PAECs with human peripheral blood polymorphonuclear leukocytes (PMNs) caused a significant increase in EDGF release as assessed by [3H]thymidine incorporation into BALB/c 3T3 mouse fibroblasts and cell proliferation assay. The effect was time dependent and correlated with the number of PMNs, reaching a maximum with a 1:1 PAEC to PMN ratio. Generation of mitogenic activity was prevented by cycloheximide, indicating a requirement for de novo protein synthesis. Antibody-mediated inhibition assays suggested that mitogenic activity was due to platelet-derived growth factor and basic fibroblast growth factor. When supernatant from N-formyl-methionyl-leucyl-phenylalanine-stimulated PMNs was substituted for PMNs during incubation with PAECs, powerful mitogenic activity was generated, indicating the involvement of soluble mediators. A role for free oxygen radicals was ruled out by experiments in which superoxide dismutase and catalase did not prevent the increase in mitogenic activity. By contrast, serine protease inhibitors such as soybean trypsin inhibitor, alpha 1-antitrypsin, and eglin C reduced the PMN-stimulating activity by 70%, 80%, and 100%, respectively. The possible involvement of cathepsin G and elastase was investigated. Cathepsin G and elastase, when substituted for PMNs, increased the release of EDGFs in a dose-dependent fashion, mimicking the effect of PMNs. These findings suggest a new role for leukocyte-vessel wall interactions in the proliferative feature of atherosclerosis.
Authors:
L Totani; A Piccoli; G Pellegrini; A Di Santo; R Lorenzet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association     Volume:  14     ISSN:  1049-8834     ISO Abbreviation:  Arterioscler. Thromb.     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-02-04     Completed Date:  1994-02-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9101388     Medline TA:  Arterioscler Thromb     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  125-32     Citation Subset:  IM    
Affiliation:
Antonio Taticchi Unit for Atheroselerosis and Thrombosis Research, Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta
Cathepsin G
Cathepsins / pharmacology
Cell Survival
Cells, Cultured
Endothelium, Vascular / cytology,  secretion*
Fibroblast Growth Factor 2 / secretion
Free Radical Scavengers
Growth Substances / secretion*
Humans
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Neutrophils / physiology*
Pancreatic Elastase / pharmacology
Platelet-Derived Growth Factor / secretion
Protease Inhibitors / pharmacology
Reactive Oxygen Species
Serine Endopeptidases
Swine
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Growth Substances; 0/Platelet-Derived Growth Factor; 0/Protease Inhibitors; 0/Reactive Oxygen Species; 103107-01-3/Fibroblast Growth Factor 2; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; EC 3.4.-/Cathepsins; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.20/CTSG protein, human; EC 3.4.21.20/Cathepsin G; EC 3.4.21.20/Ctsg protein, mouse; EC 3.4.21.36/Pancreatic Elastase

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