Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City.
Platelet-derived growth factor (PDGF) and its receptor system regulate mesenchymal cell proliferation. We recently reported that emission-source fly-ash particles and asbestos fibers induce the PDGF alpha-receptor through a macrophage-dependent pathway, and upregulation of this receptor greatly enhances the mitogenic response of lung myofibroblasts to PDGF (Lindroos and colleagues, Am. J. Respir. Cell Mol. Biol. 1997;16:283-292). In the present study we investigated the effect of particulate matter <= 10 micrometers in size (PM10) from the southern, central, and northern regions of Mexico City on PDGF receptor induction and compared these urban, ambient particles with Mt. St. Helen's volcanic ash particles as a negative control. All Mexico City PM10 samples, but not volcanic ash, stimulated rat alveolar macrophages to secrete a soluble, upregulatory factor(s) for the PDGF alpha-receptor on early passage rat lung myofibroblasts. The macrophage-derived upregulatory activity was blocked by the interleukin (IL)-1 receptor antagonist. The ability of PM10 to stimulate IL-1beta release was blocked in part by a recombinant endotoxin neutralizing protein (rENP). Lipopolysaccharide/endotoxin (LPS) and vanadium, both constituents that were present within these PM10 samples, also stimulated macrophages to secrete factor(s) that upregulated PDGF-Ralpha on lung myofibroblasts. Direct exposure of myofibroblasts to PM10 also elicited upregulation of the PDGF alpha-receptor, and this effect was blocked by rENP and mimicked by LPS, but not vanadium. These findings suggest that PM10 particles induce expression of the PDGF receptor system through macrophage-dependent and -independent mechanisms involving endotoxin and metals.
Airway Inflammation Section, Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. bonnerj@niehs.nih.gov
J C
JC
Bonner
A B
AB
Rice
P M
PM
Lindroos
P O
PO
O'Brien
K L
KL
Dreher
I
I
Rosas
E
E
Alfaro-Moreno
A R
AR
Osornio-Vargas
D000393:Air Pollutants / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002947:Cities; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004731:Endotoxins / Q000276:immunology; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008800:Mexico; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D017968:Vanadium Compounds / Q000276:immunology / Q000494:pharmacology; D018707:Volcanic Eruptions
D000393:Air Pollutants; D017077:Culture Media, Conditioned; D004731:Endotoxins; D007375:Interleukin-1; D017968:Vanadium Compounds; C066075:vanadium pentoxide; D017479:Receptors, Platelet-Derived Growth Factor