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X Y Li

Publications and source records attributed to X Y Li.

At least 91 records · Page 5Linked to original sources
PubMed1998

Keratinocyte-specific retinoid regulation of human cellular retinoic acid binding protein-II (hCRABPII) gene promoter requires an evolutionarily conserved DR1 retinoic acid-responsive element.

Transcription of the hCRABPII gene is retinoid inducible in human skin keratinocytes (KC) but, surprisingly, not in cultured cells. The promoter for the gene harbors three putative nuclear receptor binding sites: DR5, upstream of the transcription start site; DR1 (DR1d), distal to the site; and DR1 (DR1p), a proximal variant. DR1d, but not DR1p, is conserved between human and mouse. Although DR5 has been found to be a retinoid receptor target in COS-1 cells, the function of DR1 remains unknown. We examined the functions of these DR in retinoid regulation of the hCRABPII promoter in human KC. In reporter gene assays, no significant retinoid response was observed in the promoter in cultured KC; however, overexpression of retinoid receptor heterodimers RARgamma x RXRalpha restored the response. Gel supershift assays showed that endogenous RARgamma x RXRalpha levels are much lower in cultured KC than in skin in vivo. Ligand-binding assays showed that cultured KC contain only one-third of the level of retinoic acid receptor (RAR) and one-eighth of the level of retinoid X receptor found in KC in skin. Deletion of the DR1d or DR5 sites reduced retinoid-induced promoter activity by 63% and 27%, respectively. Isolated DR1d and DR5 sites, but not DR1p, efficiently bound RARgamma-RXRalpha and conferred RAR-selective retinoid responsiveness on a heterologous promoter. These data indicate that: (i) the previously reported lack of retinoid regulation of endogenous hCRABPII gene transcription in cultured KC is likely due to insufficient levels of RARgamma x RXRalpha, but not their cofactors; (ii) the conserved DR1d site is the major functional target in RARgamma x RXRalpha regulation of hCRABPII in KC; (iii) the DR1p site is nonfunctional due to its lack of affinity for RARgamma x RXRalpha, although its half-sites share high sequence homology with the consensus retinoid receptor-binding half-site.

Base Sequence↗
PubMed1998

Aqueous humor-borne factor upregulates Bcl-2 expression in corneal endothelial cells.

PURPOSE: To determine if factors present in the aqueous humor (AH) protect the corneal endothelium from apoptosis. METHODS: Mouse and human corneal endothelial cells were cultured in vitro, and apoptosis was induced by nutrient deprivation. AH and supernatant from iris/ciliary body (I/CB) cell cultures were tested for their effect on corneal endothelial cell apoptosis. The effect of I/CB supernatant on Fas, Bax, and Bcl-2 gene transcription was evaluated by Northern blotting. I/CB supernatant was subjected to proteinase analysis to identify the apoptosis inhibitory factor(s). RESULTS: Rabbit AH and supernatant from mouse I/CB cell cultures inhibited the apoptosis of mouse and human immortalized corneal endothelial cell lines. The inhibition of apoptosis was associated with an upregulation of Bcl-2 gene transcription and Bcl-2 protein expression. Bax gene expression was not significantly affected by I/CB cell supernatant. Induction of apoptosis by stimulation of the Fas receptor was unaffected by I/CB cell supernatant. Protease analyses indicated that the apoptosis inhibitory factor was a protein. CONCLUSIONS: The inability of corneal endothelial cells to undergo mitosis renders the corneal endothelium vulnerable to loss of physiological function through cellular attrition. However, a protein(s) produced by I/CB cells and present in the AH, upregulates Bcl-2 gene transcription and protects the corneal endothelial cells from apoptosis.

Animals↗
PubMed1998

Mucosal and parenteral vaccination against acute and latent murine cytomegalovirus (MCMV) infection by using an attenuated MCMV mutant.

We used a live attenuated murine cytomegalovirus (MCMV) mutant to analyze mechanisms of vaccination against acute and latent CMV infection. We selected MCMV mutant RV7 as a vaccine candidate since this virus grows well in tissue culture but is profoundly attenuated for growth in normal and severe combined immunodeficient (SCID) mice (V. J. Cavanaugh et al., J. Virol. 70:1365-1374, 1996). BALB/c mice were immunized twice (0 and 14 days) subcutaneously (s.c.) with tissue culture-passaged RV7 and then challenged with salivary gland-passaged wild-type MCMV (sgMCMV) intraperitoneally (i.p.) on day 28. RV7 vaccination protected mice against challenge with 10(5) PFU of sgMCMV, a dose that killed 100% of mock-vaccinated mice. RV7 vaccination reduced MCMV replication 100- to 500-fold in the spleen between 1 and 8 days after challenge. We used the capacity to control replication of MCMV in the spleen 4 days after challenge as a surrogate for protection. Protection was antigen specific and required both live RV7 and antigen-specific lymphocytes. Interestingly, RV7 was effective when administered s.c., i.p., perorally, intranasally, and intragastrically, demonstrating that attenuated CMV applied to mucosal surfaces can elicit protection against parenteral virus challenge. B cells and immunoglobulin G were not essential for RV7-induced immunity since B-cell-deficient mice were effectively vaccinated by RV7. CD8 T cells, but not CD4 T cells, were critical for RV7-induced protection. Depletion of CD8 T cells by passive transfer of monoclonal anti-CD8 (but not anti-CD4) antibody abrogated RV7-mediated protection, and RV7 vaccination was less efficient in CD8 T-cell-deficient mice with a targeted mutation in the beta2-microglobulin gene. Although gamma interferon is important for innate resistance to MCMV, it was not essential for RV7 vaccination since gamma interferon receptor-deficient mice were protected by RV7 vaccination. Establishment of and/or reactivation from latency by sgMCMV was decreased by RV7 vaccination, as measured by diminished reactivation of MCMV from splenic explants. We found no evidence for establishment of splenic latency by RV7 after s.c. vaccination. We conclude that RV7 administered through both systemic and mucosal routes is an effective vaccine against MCMV infection. It may be possible to design human CMV vaccines with similar properties.

Animals↗
PubMed1998

Lipopolysaccharide-induced alveolar epithelial permeability: the role of nitric oxide.

Intratracheal instillation of lipopolysaccharide (LPS) in the rat has been used as a model of acute lung inflammation. Among the early events in this process is a transient increase in airspace epithelial permeability which peaks 4 h after intratracheal instillation of LPS. The increased epithelial permeability is concomitant with the influx of neutrophils into the airspaces, peaking 8 h postinstillation. We have investigated the mechanism of this LPS-induced increase in epithelial permeability. The role of the neutrophil in LPS-induced epithelial permeability was assessed by pretreatment with neutrophil antibody to abolish neutrophil influx, which did not affect the increase in epithelial permeability. Because LPS instillation also induced increased tumor necrosis factor alpha (TNF-alpha) activity in bronchoalveolar lavage (BAL) fluid, and its release by cultured BAL leukocytes from treated animals, TNF-alpha antibody was coinstilled intratracheally with LPS in rats. TNF-alpha antibody eliminated TNF-alpha activity in BAL fluid, but had no effect on LPS-induced increased epithelial permeability. Increased levels of nitric oxide (NO), measured as nitrite, were also present in BAL fluid from LPS-treated rat lungs and LPS-elicited BAL leukocytes produced increased NO in culture. Treatment of rats with the specific NO synthase inhibitor L-NMMA significantly diminished the LPS-induced increased epithelial permeability. These data suggest that NO is involved in LPS-induced changes in epithelial integrity. However, other mechanisms should be evoked in addition to NO to explain completely the increased epithelial permeability produced by LPS.

Animals↗
PubMed1998

Cytokine and nitric oxide production by rat microglia stimulated with lipopolysaccharides in vitro.

AIM: To study the characterization of interleukin (IL)-1, IL-2, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production in microglia stimulated with lipopolysaccharides (LPS). METHODS: Primary cultured neonatal rat microglia were incubated with LPS (0-10 mg.L-1) for 0-72 h. The supernatants and lysates were collected. IL-1, IL-2, and TNF-alpha were assayed by mouse thymocyte proliferation, mouse spleen cell proliferation, and 1929 cytotoxity, respectively. NO was assayed by Griess reaction. RESULTS: Extracellular IL-1, TNF-alpha, and NO production reached peak levels at LPS 1 mg.L-1. Intracellular IL-1 production reached its peak level at LPS 100 micrograms.L-1. Intracellular TNF-alpha level was very low. IL-1, TNF-alpha, and NO activities were detected at 1, 4, and 8 h, after the cells were stimulated with LPS. IL-1 got to its peak value at 8 h, TNF-alpha, and NO reached the highest levels at 24 h. However, IL-2 activity was not detected after the microglia were stimulated with LPS 0-10 mg.L-1 during the incubation period. CONCLUSION: Rat microglia stimulated with LPS in vitro produced proinflammatory cytokines and NO.

Animals↗
PubMed1998

Immunomodulating effects of methionine enkephalin.

Methionine enkephalin (Met-Enk), the endogenous neuropeptide, is suggested to be involved in the regulatory loop between immune and neuroendocrine systems. Our studies showed that Met-Enk over a wide range of concentrations increased interleukin-1 (IL-1) production from mouse peritoneal macrophages induced by lipopolysaccharides (LPS) and naloxone did not block the enhancing effect. Met-Enk promoted the proliferation of mouse splenocyte and the production of IL-2 and IL-6 in a dose-dependent manner. The up-regulating effects of IL-2 and IL-6 not only augmented their mRNA transcription but also increased their stability. Thus Met-Enk appears to be an important immunomodulatory signaling molecule to exert regulatory actions concerned with the expressing of pre-inflammatory cytokines.

Animals↗
PubMed1998

Inhibitory effects of ginkgolides on nitric oxide production in neonatal rat microglia in vitro.

AIM: To study the effects of ginkgolide A (GA) and B (GB), apafant (Apa), and N omega-nitro-L-arginine (L-NA) on nitric oxide (NO) production in cultured neonatal rat microglia. METHODS: NO concentration was represented by nitrite which was determined by Griess reaction. RESULTS: In resting microglia, no inhibitory effects of GA, GB, and Apa were observed. L-NA inhibited NO production, its IC50 value (95% confidence limits) being 3.4 (0.8-14.9) mumol.L-1. GA, GB, and L-NA inhibited NO production in LPS-stimulated microglia, and their IC50 values (95% confidence limits) were 5.7 (1.8-18.1), 1.1 (0.3-4.4), and 0.5 (0.1-2.8) mumol.L-1, respectively. Apa did not inhibit NO production. CONCLUSION: GA and GB inhibited NO production in LPS-stimulated microglia.

Animals↗
PubMed1998

Immunologic phenotype of hosts orally immunized with corneal alloantigens.

PURPOSE: To evaluate the immunologic phenotype of hosts tolerized by oral administration of corneal alloantigens. METHODS: CB6F1 mice were tolerized by oral administration of allogeneic C3H/Hej corneal epithelial and endothelial cells before receiving heterotopic C3H/Hej corneal allografts. C3H-specific cytotoxic T-lymphocyte (CTL), delayed-type hypersensitivity (DTH), and mixed-lymphocyte responses were evaluated in orally tolerized and control mice. Cytokine profiles of Peyer's patch cells from orally tolerized mice were determined by enzyme-linked immunosorbent assay and mink lung cell culture bioassay. RESULTS: Oral administration of corneal cells produced a profound inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses. Conjugation with the B subunit of cholera toxin markedly increased the tolerizing activity of corneal endothelial cells, so that a single dose of cholera toxin-conjugated corneal cells inhibited alloimmune responses to the same degree as 10 doses of corneal cells unconjugated with cholera toxin. Peyer's patch cells from orally tolerized mice produced reduced quantities of interferon-gamma and interleukin-2 but produced increased amounts of transforming growth factor-beta and interleukin-10 compared with concentrations in normal control animals. CONCLUSIONS: Oral administration of cholera toxin-conjugated corneal cells produces a dose-dependent inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses. Orally induced inhibition of cell-mediated immune responses to corneal alloantigens is correlated with a sharp increase in the secretion of transforming growth factor-beta and interleukin-10 and a concomitant suppression of interleukin-2 and interferon-gamma. The well-recognized immunosuppressive characteristics of transforming growth factor-beta and interleukin-10 are suggestive that orally induced tolerance to corneal alloantigens is mediated by these cytokines.

Administration, Oral↗
PubMed1998

Effects of ginkgolides on interleukin-1, tumor necrosis factor-alpha and nitric oxide production by rat microglia stimulated with lipopolysaccharides in vitro.

The effects of ginkgolide A (CAS 15291-75-5, BN52020, GA) and B (CAS 15291-77-7, BN52021, GB) on interleukin (IL)-1, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production in resting and lipopolysaccharide (LPS)-stimulated neonatal rat microglia were studied. Apafant (CAS 105219-56-5), a platelet activating factor (PAF) antagonist of triazolobenzodiazepine type was used as control. The biological activities of IL-1 and TNF-alpha were tested by mouse thymocyte proliferation and L929 cytotoxicity assay, respectively. NO concentration was represented by nitrite and determined by Griess reaction. GA 1 nmol/1-10 mumol/l inhibited IL-1 production, and 100 nmol/l-10 mumol/l decreased TNF-alpha and NO production in dose-dependent manner. GB inhibited IL-1, TNF-alpha and NO production at the concentrations 10 nmol/l-10 mumol/l, 100 nmol/l-10 mumol/l and 10 nmol/l-10 mumol/l, respectively. Apafant inhibited IL-1, but not TNF-alpha and NO production. GB plus apafant (50 mumol/l) showed IL-1 and NO inhibitory effects, but not on TNF-alpha. The manner was different from that of GB or apafant alone. The results suggested that GA and GB inhibited proinflammatory cytokines and NO production from LPS-stimulated rat microglia, however, apafant inhibited IL-1 production only. The effects of GA and GB on proinflammatory cytokines and NO production from rat microglia do not seem to be based on PAF receptor antagonism. In addition, GA and GB are regarded as promising agents for the treatment of some neurodegenerative diseases in the central nervous system.

Animals↗
PubMed1997

Inhibition of metastasis of intraocular melanomas by adenovirus-mediated gene transfer of plasminogen activator inhibitor type 1 (PAI-1) in an athymic mouse model.

Uveal melanoma is the most common intraocular malignancy in adults and results in the death of 50% of the patients. Plasminogen activators (PA) are believed to facilitate tumor metastasis by promoting invasion of tissue barriers. The present study explored the possibility of preventing the metastasis of intraocular melanomas by disrupting plasminogen activator function through gene transfer. A replication-deficient adenovirus vector was used for the in vivo transfer of plasminogen activator inhibitor type 1 (PAI-1) cDNA. Intraocular injection of an adenovirus vector (AdCMV-PAI-1) expressing plasminogen activator inhibitor-1 resulted in: (1) the transduction of more than 95% of human and murine uveal melanoma cells in the eyes of nude mice; (2) a 50% reduction in the number of animals developing liver metastases; and (3) a 78% reduction in the metastatic tumor burden in animals that eventually developed metastases. In other experiments intravenous injections of AdCMV-PAI-1 resulted in transduction of normal liver cells and culminated in a sharp reduction in the incidence of metastases and a significant prolongation of host survival. The results support the feasibility of disruption of PA function through gene transfer as a therapeutic strategy for preventing metastases and prolonging host survival.

Adenoviruses, Human↗
PubMed1997

Suprabasal expression of a dominant-negative RXR alpha mutant in transgenic mouse epidermis impairs regulation of gene transcription and basal keratinocyte proliferation by RAR-selective retinoids.

To determine whether 9-cis retinoic acid receptors (RXRs) regulate the biological activity of all-trans retinoic acid (tRA) and its receptors (RARs) in skin, we have targeted a dominant-negative RXR alpha (dnRXR alpha) lacking transactivation function AF-2 to differentiated suprabasal keratinocytes in the epidermis of transgenic mice. Driven by the suprabasal-specific keratin-10 gene promoter, expression of dnRXR alpha severely reduced the ability of RAR-selective ligands tRA and CD367 to induce epidermal mRNA levels of the CRABPII, CRBPI, and CRBPII genes, which contain RA-responsive elements (RAREs) DR1 and/or DR2. It also reduced gene-specific, synergistic induction of CRBPI mRNA by a combination of CD367 and RXR-selective SR11237. Like endogenous RXR alpha, dnRXR alpha in epidermal nuclear extracts from the transgenic mice competitively formed heterodimers with endogenous RAR gamma on RAREs, suggesting that dnRXR alpha impairs retinoid signaling by competing with endogenous RAR gamma-RXR alpha heterodimers. Histologically, the epidermis of dnRXR alpha mice showed no detectable developmental abnormalities. Surprisingly, in adult animals, the suprabasal expression of dnRXR alpha significantly reduced the ability of topically applied tRA to stimulate proliferation of undifferentiated keratinocytes in the basal layer of epidermis. RXR-selective ligands alone had no detectable effects on both normal and transgenic mouse epidermis. Accordingly, we suggest that in vivo: (1) in suprabasal keratinocytes, retinoids regulate gene transcription via RAR-RXR heterodimers in which RAR confers a predominant ligand response, whereas RXR AF-2 is required for liganded RAR AF-2 to efficiently trans-activate target genes, and (2) this suprabasal RXR-assisted mechanism indirectly regulates proliferation of basal keratinocytes likely via intercellular signaling.

Animals↗
PubMed1997

Novel transient outward K+ current of mature murine hippocampal neurones.

Hippocampal neurones were freshly isolated from the brain of adult mice and voltage-dependent K+ currents were recorded with whole-cell patch-clamp technique. Three components of transient K+ current (IA) were isolated when analyzing data with exponential functions or treating neurones with a variety of voltage protocols and pharmacologic agents. Subtraction of the delayed rectifier current (IK) from the K+ currents elicited after prepulses to -120 mV of varying duration revealed fast (IAf) and slow (IAs) components with decay time constants of 45 +/- 8 and 612 +/- 140 ms, respectively; the corresponding time constants for the removal of inactivation were 12.3 and 189.6 ms. both tetraethylammonium and dendrotoxin selectively inhibited IAs. 4-Aminopyridine (4-AP) specifically blocked IAf and 40% of IAs with different affinities. Therefore, the properties of a 4-AP-resistant (IAsR) and 4-AP-sensitive (IAsS) component of IAs were compared. These data suggest that three distinct subtypes of K+ currents contribute to the IA of mature murine hippocampal neurones.

4-Aminopyridine↗
PubMed1997

Retinoid X receptor-specific ligands synergistically upregulate 1, 25-dihydroxyvitamin D3-dependent transcription in epidermal keratinocytes in vitro and in vivo.

We have examined the mechanism by which endogenous retinoid X receptor (RXR), vitamin D3 receptor (VDR), and cognate ligands regulate nuclear 1,25-dihydroxyvitamin D3 (D3) signaling in epidermal keratinocytes from skin, a physiologic D3 target. In vitro, RXR and VDR-specific antibodies identified endogenous RXR and VDR bound to a vitamin D3-responsive element (DR3) as heterodimers (VDR-RXR). In cultured keratinocytes, 9-cis retinoic acid (9cRA), a panagonist for RXR and retinoic acid receptor (RAR), and an RXR-selective agonist, SR11237, synergized with D3 to activate DR3 via endogenous as well as overexpressed VDR-RXR, whereas both of these RXR agonists alone were ineffective. In contrast, SR11237 did not synergize with but antagonized an RAR-selective ligand activation of a retinoic acid-responsive element (DR5) via endogenous RAR-RXR. Furthermore, expression of RXR mutated in transactivation domain AF-2 inhibited endogenous VDR-RXR activity over DR3. This mutant efficiently bound to DR3 as VDR-RXR but showed reduced capacity to transactivate DR3 in response to D3 and SR11237. In vivo, D3 and SR11237 synergistically induced the naturally occurring D3-responsive 24-hydroxylase gene in epidermis of mouse skin, whereas SR11237 alone was ineffective. Our data suggest that allosteric changes caused by VDR in DR3-bound VDR-RXR do not block access of ligands to RXR. RXR ligand-induced conformational changes permit VDR-RXR, via both VDR and RXR activation function domains, to mediate maximal D3 signaling in keratinocytes.

Animals↗
PubMed1997

The retinoid X receptor agonist 9-cis-retinoic acid and the 24-hydroxylase inhibitor ketoconazole increase activity of 1,25-dihydroxyvitamin D3 in human skin in vivo.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] transactivates its target genes via the vitamin D receptor (VDR). VDR functions in physiology as a dimer complexed with retinoid X receptor (RXR), whose natural ligand is 9-cis-retinoic acid (9-c-RA). Inactivation of 1,25(OH)2D3 occurs through a cytochrome P-450 24-hydroxylase (OHase). The promoter of the human 24-OHase gene contains a 1,25(OH)2D3-responsive enhancer element (VDRE). We have used this VDRE containing gene as an endogenous reporter for vitamin D3-mediated gene activation in vivo. Normal adult human skin was keratomed after a 2-d exposure to 1,25(OH)2D3, 9-c-RA, all-trans-RA, and ketoconazole. 1,25(OH)2D3 caused a concentration-dependent increase in 24-OHase mRNA expression as determined by northern blot analysis. The activity of epidermal 24-OHase was also induced by 1,25(OH)2D3. Compared with vehicle, neither of the RA isomers nor ketoconazole alone induced 24-OHase mRNA. Addition of 9-c-RA or t-RA to 1,25(OH)2D3, however, caused a synergistic increase in 24-OHase mRNA. Similarly, 1,25(OH)2D3 plus ketoconazole increased 24-OHase mRNA synergistically. Ketoconazole inhibited ex vivo 1,25(OH)2D3-induced epidermal 24-OHase activity. Thus, 24-OHase mRNA induction is a sensitive reporter of 1,25(OH)2D3 activity in vivo; RXR bound to VDR is not a silent partner in vivo, because 9-c-RA enhances 1,25(OH)2D3-liganded RXR/VDR stimulation of the VDRE containing 24-OHase gene; ketoconazole inhibition of 24-OHase enhances 1,25(OH)2D3 activity by impeding its breakdown. Thus, the synergistic response of human skin to topical 1,25(OH)2D3 and/or 1,25(OH)2D3 analogs plus RXR retinoids and/or ketoconazole may be exploited to give a desired biologic/therapeutic response with less 1,25(OH)2D3, minimizing the potential calcemic risk from systemic absorption of 1,25(OH)2D3.

Adult↗
PubMed1997

Late expression of a beta chemokine homolog by murine cytomegalovirus.

A gene (HJ1) present in murine cytomegalovirus (MCMV) encodes an open reading frame (ORF) whose predicted amino acid sequence shows homology to the beta (or C-C) class of chemotactic cytokines known as chemokines. The region of homology is located in the carboxyl-terminal portion of the 116-amino-acid ORF. A 0.9-kb RNA transcript corresponding to the HJ1 gene is expressed in MCMV-infected fibroblasts and macrophages as a member of the late kinetic class of virally encoded transcripts. A transcriptional start site is located between the third and fourth methionine residues in the ORF, predicting a primary amino acid structure, starting at the fourth methionine residue, which includes a possible signal peptide as well as conserved cysteine residues typical for mammalian beta chemokines. The RNA transcript is polyadenylated, suggesting that it can undergo translation within the cytoplasm of an MCMV-infected cell. We speculate that expression of the chemokine homolog at late times in the MCMV replication cycle plays a role in MCMV pathogenesis, possibly by action as a chemotactic agonist or antagonist or by alteration of the activation or differentiation state of a susceptible cell such as a macrophage.

Amino Acid Sequence↗
PubMed1997

In vivo and in vitro proinflammatory effects of particulate air pollution (PM10).

Epidemiologic studies have reported associations between fine particulate air pollution, especially particles less than 10 mm in diameter (PM10), and the development of exacerbations of asthma and chronic obstructive pulmonary disease. However, the mechanism is unknown. We tested our hypothesis that PM10 induces oxidant stress, causing inflammation and injury to airway epithelium. We assessed the effects of intratracheal instillation of PM10 in rat lungs. The influx of inflammatory cells was measured in bronchoalveolar lavage (BAL). Airspace epithelial permeability was assessed as total protein in bronchoalveolar lavage fluid (BALF) in vivo. The oxidant properties of PM10 were determined by their ability to cause changes in reduced glutathione (GSH) and oxidized glutathione (GSSG). We also compared the effects of PM10 with those of fine (CB) and ultrafine (ufCB) carbon black particles. Six hours after intratracheal instillation of PM10, we noted an influx of neutrophils (up to 15% of total BAL cells) in the alveolar space, increased epithelial permeability, an increase in total protein in BALF from 0.39 +/- 0.01 to 0.62 +/- 0.01 mg/ml (mean +/- SEM) and increased lactate dehydrogenase concentrations in BALF. An even greater inflammatory response was observed after intratracheal instillation of ufCB, but not after CB instillation. PM10 had oxidant activity in vivo, as shown by decreased GSH in BALF (from 0.36 +/- 0.05 to 0.25 +/- 0.01 nmol/ml) after instillation. BAL leukocytes from rats treated with PM10 produced greater amounts of nitric oxide, measured as nitrite (control 3.07 +/- 0.33, treated 4.45 +/- 0.23 mM/1 x 10(6) cells) and tumor necrosis factor alpha (control 21.0 +/- 3.1, treated 179.2 +/- 29.4 unit/1 x 10(6) cells) in culture than BAL leukocytes obtained from control animals. These studies provide evidence that PM10 has free radical activity and causes lung inflammation and epithelial injury. These data support our hypothesis concerning the mechanism for the adverse effects of particulate air pollution on patients with airway diseases.

Air Pollutants↗