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PubMed1999

Normalization of hyperglycaemia by oral vanadyl sulfate does not reverse diabetes-induced protection against cisplatin nephrotoxicity in streptozotocin-diabetic rats.

Streptozotocin- and galactose-induced diabetic rats are protected against nephrotoxic effects of cisplatin. While the mechanism remains to be defined, protection is associated with a decrease in the accumulation of platinum in renal cortical tissues of streptozotocin-diabetic versus non-diabetic rats. A physiological abnormality common to streptozotocin and galactosemic models of diabetes is hyperglycaemia, suggesting that elevated sugars are involved in mediating protection of diabetic kidney against cisplatin nephrotoxicity. The current study focused on the effect of normalization of hyperglycaemia by vanadyl sulfate trihydrate on the initiation of protection and accumulation of platinum in kidneys of streptozotocin-diabetic rats. Streptozotocin-diabetic rats were treated with 0.75 mg/ml of vanadyl sulfate trihydrate in drinking water to normalize streptozotocin-induced hyperglycaemia. Vanadyl sulfate treatment normalized plasma glucose and glycosylated haemoglobin levels in streptozotocin-diabetic rats to values observed for non-diabetic rats. Intraperitoneal administration of cisplatin (5 mg/kg body weight) increased blood urea nitrogen by a factor >2.5 over baseline in both untreated and vanadyl-treated non-diabetic groups. Cisplatin-induced increases in blood urea nitrogen were 1.6 times baseline in both untreated and vanadyl-treated streptozotocin-diabetic rats. Renal platinum accumulation was significantly lower in streptozotocin-diabetic versus non-diabetic rats regardless of vanadyl sulfate treatment. Renal vanadium levels in all groups of diabetic rats were not significantly different from each other. These results indicate that normalization of plasma glucose levels with vanadyl sulfate in streptozotocin-diabetic rats did not reverse protection of streptozotocin-diabetic kidney against cisplatin nephrotoxicity.

Administration, Oral↗
PubMed1996

The effect of oral vanadyl sulfate on body composition and performance in weight-training athletes.

The effects of oral vanadyl sulfate (VOSO4) (0.5 mg/kg/day) on anthropometry, body composition, and performance were investigated in a 12-week, double-blind, placebo-controlled trial involving weight-training volunteers. Performance was assessed in the treatment (VS) and placebo (P) groups using 1 and 10 repetitions maximum (RM) for the bench press and leg extension. Thirty-one subjects completed the trial, with 2 VS subjects withdrawing because of apparent side effects. There were no significant treatment effects for anthropometric parameters and body composition during the trial. Both groups had significant improvements in performance but the only significant effect of treatment was a Treatment x Time interaction in the 1 RM leg extension (p = .002), which could have arisen because the VS group had a lower performance at baseline in this test. It was concluded that oral vanadyl sulfate was ineffective in changing body composition in weight-training athletes, and any modest performance-enhancing effect requires further investigation.

Absorptiometry, Photon↗
PubMed2004

Antiretroviral spermicide WHI-07 prevents vaginal and rectal transmission of feline immunodeficiency virus in domestic cats.

WHI-07 [5-bromo-6-methoxy-5,6-dihydro-3'-azidothymidine-5'-(p-bromophenyl)-methoxy alaninyl phosphate] is a novel dual-function aryl phosphate derivative of zidovudine with potent anti-human immunodeficiency virus (HIV) and spermicidal activities. WHI-07 was active against the feline immunodeficiency virus (FIV). This study evaluated whether topical application of WHI-07 as a single agent and in combination with an organometallic vanadium complex, vanadocene dithiocarbamate (VDDTC), via a nontoxic gel microemulsion can block vaginal as well as rectal transmission of feline AIDS (FAIDS) by chronically FIV-infected feline T cells in the natural host model. Genital transmission of FIV was monitored in recipient cats by the appearance of viral antibodies to FIV Gag proteins and by virus isolation of blood leukocytes as measured by FIV reverse transcriptase activity and FIV-specific PCR. Microbicidal activity was considered effective when the treated cats did not show evidence of FIV infection for up to 18 weeks postchallenge. An aggregate analysis of 46 specific-pathogen-free cats revealed that a single dose of the infected cell inoculum efficiently transmitted FIV infection when delivered into the vagina (100%) or rectum (66%). Pretreatment of the vagina or rectum with 2% WHI-07 alone or in combination with 0.25% VDDTC significantly (P = 0.004) protected cats from genital transmission by the highly infectious inoculum (7 million FIV(Bangston)-infected feline T cells). Collectively, using the vaginal and rectal transmucosal model for FAIDS, our studies demonstrated that WHI-07 either alone or in combination with a vanadocene has clinical potential for the development of a dual-function anti-HIV microbicide for sexually active women.

Animals↗
PubMed1989

Genetic evidence for an Azotobacter vinelandii nitrogenase lacking molybdenum and vanadium.

We have constructed a strain of Azotobacter vinelandii which has deletions in the genes for both the molybdenum (Mo) and vanadium (V) nitrogenases. This strain fixed nitrogen in medium that did not contain Mo or V. Growth and nitrogenase activity were inhibited by Mo and V. In highly purified medium, growth was limited by iron. Addition of other metals (Co, Cr, Cu, Mn, Ni, Re, Ti, W, and Zn) did not stimulate growth. Like the V-nitrogenase, the nitrogenase synthesized by the double deletion strain reduced acetylene to both ethylene and ethane (C2H6/C2H4 ratio, 0.046). There was an approximately 10-fold increase in ethane production when Mo was added to the deletion strain grown in medium lacking Mo and V. This change in reactivity may be due to the incorporation of an Mo-containing cofactor into the nitrogenase synthesized by the double-deletion strain. A strain synthesizing the V-nitrogenase did not show a similar increase in ethane production. The growth characteristics of the double-deletion strain, together with the metal composition reported for a nitrogenase isolated from a tungstate-tolerant strain lacking genes for the molydenum enzyme grown in the absence of Mo and V (J. R. Chisnell, R. Premakumar, and P. E. Bishop, J. Bacteriol. 170:27-33, 1988) show that A. vinelandii can synthesize a nitrogenase which lacks both Mo and V. Reduction of dinitrogen by nitrogenase can therefore occur at a center lacking both these metals.

Azotobacter↗
PubMed1995

Upper airway response in workers exposed to fuel oil ash: nasal lavage analysis.

OBJECTIVES: Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS: A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS: Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION: A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.

Adult↗
PubMed1985

Vanadium exposure enhances lipid peroxidation in the kidney of rats and mice.

Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues. In both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.

Animals↗
PubMed2006

Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway.

The multifunctional cell-surface protein dipeptidyl peptidase IV (DPPIV/CD26) is aberrantly expressed in many cancers and plays a key role in tumorigenesis and metastasis. Its diverse cellular roles include modulation of chemokine activity by cleaving dipeptides from the chemokine NH(2)-terminus, perturbation of extracellular nucleoside metabolism by binding the ecto-enzyme adenosine deaminase, and interaction with the extracellular matrix by binding proteins such as collagen and fibronectin. We have recently shown that DPPIV can be downregulated from the cell surface of HT-29 colorectal carcinoma cells by adenosine, which is a metabolite that becomes concentrated in the extracellular fluid of hypoxic solid tumors. Most of the known responses to adenosine are mediated through four different subtypes of G protein-coupled adenosine receptors: A(1), A(2A), A(2B), and A(3). We report here that adenosine downregulation of DPPIV from the surface of HT-29 cells occurs independently of these classic receptor subtypes, and is mediated by a novel cell-surface mechanism that induces an increase in protein tyrosine phosphatase activity. The increase in protein tyrosine phosphatase activity leads to a decrease in the tyrosine phosphorylation of ERK1/2 MAP kinase that in turn links to the decline in DPPIV mRNA and protein. The downregulation of DPPIV occurs independently of changes in the activities of protein kinases A or C, phosphatidylinositol 3-kinase, other serine/threonine phosphatases, or the p38 or JNK MAP kinases. This novel action of adenosine has implications for our ability to manipulate adenosine-dependent events within the solid tumor microenvironment.

Adenosine↗
PubMed1989

Oral vanadyl sulfate in treatment of diabetes mellitus in rats.

Recent reports have suggested that vanadium in the form of vanadyl (+IV) possesses insulin-like activity. Therefore, in the present study we examined the effects of administering oral vanadyl to diabetic animals. Wistar rats made diabetic with streptozotocin and age-matched controls were maintained for 10 wk in the absence and presence of vanadyl sulfate trihydrate in the drinking water. In the presence of vanadyl, decreases in rate of growth and circulating levels of insulin were the only significant alterations recorded in control animals. In contrast, diabetic animals treated with vanadyl, despite having lower body weights and insulin levels, had normal plasma concentrations of glucose, lipid, creatinine, and thyroid hormone. In addition, abnormalities in isolated working heart function and glycerol output from adipose tissue of diabetic animals were also corrected after vanadyl treatment. These results suggest that vanadium when used in the vanadyl form is effective in diminishing the diabetic state in the rat by substituting for and replacing insulin or possibly by enhancing the effects of endogenous insulin.

Administration, Oral↗
PubMed1998

Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo.

Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-R alpha is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-R alpha protein by 48 h, and immunohistochemical analysis localized PDGF-R alpha primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-R alpha in vivo preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2O5 in vitro released upregulatory activity for PDGF-R alpha on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1 beta-mediated induction of PDGF-R alpha in vivo is important to lung myofibroblast hyperplasia during fibrogenesis.

Animals↗
PubMed2000

Airway fibrosis in rats induced by vanadium pentoxide.

Vanadium pentoxide (V(2)O(5)) is a cause of occupational asthma and bronchitis. We previously reported that intratracheal instillation of rats with V(2)O(5) causes fibrosis of the lung parenchyma (J. C. Bonner, P. M. Lindroos, A. B. Rice, C. R. Moomaw, and D. L. Morgan. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L72-L80, 1998). In this report, we show that intratracheal instillation of V(2)O(5) induces airway remodeling similar to that observed in individuals with asthma. These changes include airway smooth muscle cell thickening, mucous cell metaplasia, and airway fibrosis. The transient appearance of peribronchiolar myofibroblasts, which were desmin and vimentin positive, coincided with a twofold increase in the thickness of the airway smooth muscle layer at day 6 after instillation and preceded the development of airway fibrosis by day 15. The number of nuclear profiles within the smooth muscle layer also increased twofold after V(2)O(5) instillation, suggesting that hyperplasia accounted for thickening of the smooth muscle layer. The majority of cells incorporating bromodeoxyuridine at day 3 were located in the connective tissue surrounding the airway smooth muscle wall that was positive for vimentin and desmin. These data suggest that myofibroblasts are the principal proliferating cell type that contributes to the progression of airway fibrosis after V(2)O(5) injury.

Animals↗
PubMed1995

On-line measurement of nitric oxide generation in buffer-perfused rabbit lungs.

In buffer-perfused rabbit lungs, the mixed expired gas was continuously analyzed for nitric oxide (NO) by chemiluminescence detection, and recovery data in dependency of the alveolar O2 tension were established. A small aliquot of the lung effluent was continuously forwarded to a reaction vessel in which the NO decomposition products nitrite, peroxynitrite, and nitrate [summarized as NOx; acidic vanadium (III) chloride reagent] or nitrite (acidic sodium iodide reagent) were quantitatively reduced back to NO, which was then transferred to a second chemiluminescence detector. Under baseline conditions, the perfused lungs continuously released 2.2 +/- 0.21 nmol/min of NO (n = 10) into the gas space. NO was permanently liberated into the intravascular compartment at 7.0 +/- 0.3 nmol/min (n = 4). According to a very low buffer-gas partition coefficient of NO (estimated to be 0.0292 +/- 0.005 in separate equilibration experiments), NO aerated into the prelung perfusate largely escaped into the alveolar space within one lung passage, whereas only low percentages of inhaled NO were detected as NOx in the buffer medium. Immediate increase of lung NO generation in response to A-23187 challenge and inhibition by NG-monomethyl-L-arginine were demonstrated. In conclusion, in buffer-perfused lungs, total NO generation may be monitored by continuous analysis of NO exhalation and perfusate NOx accumulation.

Animals↗
PubMed1995

The effect of aluminum on the vanadium-mediated oxidation of NADH.

Aluminum catalyzes the oxidation of NADH by vanadate both in the presence and absence of a reducing sugar. The effect of aluminum is concentration dependent and inhibitable with superoxide dismutase but not catalase. The fructose-6-phosphate-free reaction is characterized by an initial lag phase which can be eliminated by preincubating aluminum with NADH, but is not altered by preincubating aluminum with vanadate, suggesting that the effect of aluminum is not directly on vanadate. Aluminum also catalyzes vanadyl-mediated oxidation of NADH, and this effect is similarly inhibitable by superoxide dismutase as well as catalase. It is suggested that aluminum catalyzes the oxidation of NADH by vanadium though enhancing the production of superoxide radicals and that this effect may account in part of the biological toxicity associated with aluminum, particularly when associated with the accumulation of other trace elements such as vanadium.

Aluminum↗
PubMed1994

Vanadyl sulfate prevents fructose-induced hyperinsulinemia and hypertension in rats.

To determine whether insulin resistance and hyperinsulinemia are causally related to fructose-induced hypertension, we used vanadyl sulfate, a drug that improves insulin sensitivity in rats. Chronic oral vanadyl treatment was initiated in 6-week-old male Sprague-Dawley rats. One week after vanadyl was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma glucose and insulin levels and systolic blood pressure were measured weekly for 4 weeks. Fructose feeding induced hyperinsulinemia (fructose-fed, 366.6 +/- 8.4 versus control, 276 +/- 10.8 pmol/L, P < .001) and increased blood pressure (fructose-fed, 160 +/- 3.0 versus control, 124 +/- 3.0 mm Hg, P < .001). Vanadyl (0.4 to 0.6 mmol/kg per day) prevented the rise in plasma insulin (treated, 211.2 +/- 6.0 pmol/L, P < .001) and blood pressure (treated, 127 +/- 3.0 mm Hg, P < .001) in the fructose-fed rats without a change in plasma glucose. No change in blood pressure was seen in the control group. After 4 weeks, euglycemic clamps were performed on 20-hour fasted, conscious, mobile rats. Low-dose porcine insulin infusion (14 pmol/kg per minute) with concomitant somatostatin infusion resulted in similar steady-state plasma glucose and insulin levels in the various groups. Hepatic glucose production was suppressed and similar among various groups under clamp conditions. Insulin sensitivity index (micromoles of glucose per kilogram per hour per picomole per liter of insulin) was reduced in the fructose-fed rats compared with controls (fructose-fed, 0.9 +/- 0.4 versus control, 5.4 +/- 1.2, P < .002).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are hyperinsulinemic compared with their Wistar-Kyoto (WKY) controls. Since previous studies have demonstrated that vanadyl sulfate lowers insulin levels in nondiabetic rats, we used vanadyl to explore the relation between hyperinsulinemia and hypertension. In a prevention study, 5-week-old SHR and WKY rats were started on long-term vanadyl sulfate treatment. Vanadyl in doses of 0.4 to 0.6 mmol/kg per day lowered plasma insulin (252 +/- 22.8 versus 336 +/- 12.6 pmol/L, treated versus untreated, P < .01) and systolic blood pressure (158 +/- 2 versus 189 +/- 1 mm Hg, P < .001) in SHR without causing any change in plasma glucose. No changes were seen in the treated WKY rats. At 11 weeks of age, a group of untreated rats from the prevention study was started on vanadyl treatment as before. Again, vanadyl caused significant and sustained decreases in plasma insulin (264 +/- 12.6 versus 342 +/- 6.6 pmol/L, treated versus untreated, P < .001) and blood pressure (161 +/- 1 versus 188 +/- 1 mm Hg, P < .001) in SHR but had no effect in the normotensive WKY controls. Furthermore, restoration of plasma insulin in the vanadyl-treated SHR to pretreatment levels (subcutaneous insulin, 14,000 pmol/kg per day) reversed the effects of vanadyl on blood pressure (vanadyl with insulin, 190 +/- 3.0 mm Hg versus vanadyl without insulin, 152 +/- 3.0 mm Hg, P < .001). Since vanadyl treatment resulted in decreased weight gain, treated SHR were compared with a corresponding pair-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Airway obstruction in boilermakers exposed to fuel oil ash. A prospective investigation.

We prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were performed after approximately 4 wk of work on the boiler. Exposure to particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and respirable vanadium dust were estimated using daily work diaries and a personal sampling device for respirable particles. Using these estimates, we calculated average and peak exposure between pre- and postexposure tests for each subject. The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD) of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3, with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1 was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing the change in FEV1 by the average of the pre- and postexposure FEV1 values. The delta FEV1.adj was regressed, controlling age and current smoking status, on average and peak exposure to both PM10 and vanadium. There was a dose-response relationship between average and peak PM10 exposure and delta FEV1.adj: beta = -0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively. However, there was no relationship between delta FEV1.adj and respirable vanadium dust concentration. Furthermore, there was no postexposure change in nonspecific airway responsiveness. In summary, we found a significant fall in FEV1 and a dose-response relationship between delta FEV1.adj and average and peak PM10 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Molecular markers of acute upper airway inflammation in workers exposed to fuel-oil ash.

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 micro(m) (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.

Adult↗
PubMed1998

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.

Air Pollutants↗