In vitro effects of pentoxifylline on smooth muscle cell migration and blood monocyte production of chemotactic activity for smooth muscle cells: potential therapeutic benefit in the adult respiratory distress syndrome.
The adult respiratory distress syndrome (ARDS) is a severe lung condition characterized by an acute lung injury leading to a massive intra-alveolar fibrosis with rapid lung failure. ARDS intra-alveolar fibrosis results from the migration of mesenchymal cells (mainly smooth muscle cells [SMC]) into the alveoli through alveolar epithelial basement membrane gaps resulting from the injury. SMC migration is followed by their replication and production of extracellular matrix, which leads to fibrosis. Thus, any pharmacologic agent able to prevent SMC migration should prevent, at least in part, intra-alveolar fibrosis. SMC migration is thought to be due to the presence, in the alveolar spaces, of chemotactic factors for mesenchymal cells, such as fibronectin and platelet-derived growth factor (PDGF). The local presence of these chemotactic factors can be due to plasmatic leakage, platelet degranulation, and mononuclear phagocyte activation. Pentoxifylline is a methylxanthine interacting with the biology of several types of cells, including red blood cells, neutrophils, blood monocytes, and endothelial cells. Pentoxifylline prescription has been suggested in ARDS with respect to its activity on neutrophils, its inhibition of tumor necrosis factor-alpha (TNF) release by mononuclear phagocytes, and its prevention of TNF-induced lung injury. Since pentoxifylline can modulate the migration of several cell types, we hypothesized that it could interfere with mesenchymal cell migration. SMC migratory response was measured in vitro with modified Boyden chemotactic chambers in the presence of PDGF, fibronectin, "platelet extract," and activated blood monocyte supernatants. Pentoxifylline, at therapeutic levels, significantly reduced SMC migration in response to the presence of these chemotactic activities.(ABSTRACT TRUNCATED AT 250 WORDS)
Kullmann
A
A
INSERM U. 14, CLERC Poumon, CHU, Nancy-Vandoeuvre, France.
Vaillant
P
P
Muller
V
V
Martinet
Y
Y
Martinet
N
N
D001792:Blood Platelets; D002455:Cell Division / Q000187:drug effects; D002457:Cell Extracts / Q000494:pharmacology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000096:biosynthesis*; D002633:Chemotaxis / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology* / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
D002457:Cell Extracts; D002630:Chemotactic Factors; D005353:Fibronectins; D010982:Platelet-Derived Growth Factor; D010431:Pentoxifylline