Induction of the Lung Myofibroblast PDGF Receptor System by Urban Ambient Particles from Mexico City

Abstract

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.

Does the Harvard/U.S. Environmental Protection Agency Ambient Particle Concentrator Change the Toxic Potential of Particles?

“…17 MSHA also has been used as a negative control particle in a number of in vitro studies, including studies on pulmonary macrophage activation by complement, 22 activation of human bronchial epithelial cells, 23 and induction of the lung myofibroblast PDGF receptor system. 24 These results concur with previous findings that characterize MSHA as benign. More significantly, because of a lack of any significant difference between exposure groups and the fact that the study had sufficient power to detect differences of interest, we conclude that amorphous silicates are not altered by passage through the HAPC and that they remain benign upon inhalation exposure.…”

The Measurement of Ambient Bioaerosol Exposure

“…The exact constituents of PM air pollution that induce disease and the mechanisms involved are unknown. Studies to determine the components of PM that contribute to airway inflammation and irritation have been attempted (Bonner et al 1998;Donaldson and MacNee 2001;Soukup and Becker 2001;Boehlecke et al 2003). Aerodynamic size fractions of PM have been studied including coarse (PM 10−2.5 ) and fine (PM 2.5 ), and recently fine and submicrometer fractions (Pope 2000).…”

Aluminio en el Tracto Respiratorio Bajo de Residentes de la Ciudad de México

“…Los estudios experimentales muestran que los contaminantes del aire, en especial las partículas finas (PM 10 ) y ultrafinas (10~100 nm) penetran en los alvéolos pulmonares y pueden causar reacciones inflamatorias, (5,9), depositarse en la región toráxica (10) y vía sanguínea distribuirse a otros órganos tales como el corazón, (2,(5)(6)(7)9,11,12), e incluso al sistema nervioso central (8). Se postula que los metales transportados en la superficie de las partículas podrían ser algunos de los elementos responsables de tales efectos nocivos (2,9,13).…”

“…En ciudad de México, tanto la presencia como la cantidad de metales encontrados en las partículas del aire varía de acuerdo con la zona geográfica, (13,14). Entre los metales reportados se destaca la presencia de Al, Cu, Fe, Ti, Cr, Mn, Zn, Mo, V, Ni, Pb, (13,14).…”

“…Entre los metales reportados se destaca la presencia de Al, Cu, Fe, Ti, Cr, Mn, Zn, Mo, V, Ni, Pb, (13,14). García (14), reporta que el Al es el metal más frecuente en las partículas PM 10 y PM 2.5 de todas las zonas de la ciudad de México.…”