Analysis of bronchoalveolar lavage fluid adhering to lung surfactant. Experiment on intratracheal instillation of nickel oxide with different diameters.

Nickel oxide with two different particle sizes, micron size (NiO) and submicron size (nNiOm), as well as crystalline silica as a positive control and titanium dioxide as a negative control, were intratracheally instilled in rats and the phospholipid concentration and the protein concentration and surface tension of bronchoalveolar lavage fluid (BALF), which are used in surfactant assessment, were measured to see if they could be effective biomarkers in toxicity assessment. The results showed that the NiO instilled group showed no significant difference compared to the control group throughout the observation period. In contrast, a significant difference was found in the nNiOm instilled group compared to the control group throughout the observation period. Moreover, a significant difference was found in the crystalline silica instilled group for each measurement compared to the control group while for the titanium dioxide group, almost no significant difference was found. These results indicate that submicronsized particles of nickel oxide with smaller median diameters potentially have a stronger biological effect than micron size particles. They also indicate that screening can be done by measuring the phospholipid concentration and the protein concentration and surface tension of BALF.

The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure.

BACKGROUND: Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO(2)) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO(2) effects on surfactant ultrastructure were visualized. METHODS: A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 microg/ml) of TiO(2) NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope. RESULTS: TiO(2) NSP, but not MSP, induced a surfactant dysfunction. For TiO(2) NSP, adsorption surface tension (gammaads) increased in a dose-dependent manner from 28.2 + or - 2.3 mN/m to 33.2 + or - 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (gammamin) slightly increased from 4.8 + or - 0.5 mN/m up to 8.4 + or - 1.3 mN/m (p < 0.01) at high TiO(2) NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both gammaads (63.6 + or - 0.4 mN/m) and gammamin (21.1 + or - 0.4 mN/m). Interestingly, TiO(2) NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae. CONCLUSION: TiO(2) nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.

Amniotic fluid concentration of surfactant proteins in intra-amniotic infection.

OBJECTIVE: Pulmonary surfactant is a complex molecule of lipids and proteins synthesized and secreted by type II alveolar cells into the alveolar epithelial lining. Both lipid and protein components are essential for lung function in postnatal life. Infection is a well-established cause of preterm delivery, and several inflammatory cytokines play a role in the mechanisms of preterm parturition. An increased concentration of inflammatory cytokines in amniotic fluid or fetal plasma has been linked to the onset of preterm parturition and fetal/neonatal injury, including cerebral palsy and chronic lung disease. Experimental evidence indicates that inflammatory mediators also regulate surfactant protein synthesis, and histologic chorioamnionitis is associated with a decreased incidence of hyaline membrane disease in neonates. This study was conducted to determine if amniotic fluid concentrations of surfactant protein (SP)-A, SP-B, and SP-D change in patients with and without intra-amniotic infection (IAI). MATERIALS AND METHODS: A case-control study was conducted to determine amniotic fluid concentrations of SP-A, SP-B, SP-D, and total protein in patients who had an amniocentesis performed between 18 and 34 weeks of gestation for the detection of IAI in patients with spontaneous preterm labor with intact membranes (n = 42) and cervical insufficiency prior to the application of cerclage (n = 6). Amniotic fluid samples were selected from a bank of biological specimens and included patients with (n = 16) and without (n = 32) IAI matched for gestational age at amniocentesis. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Each group was further subdivided according to a history of corticosteroid administration within 7 days prior to amniocentesis into the following subgroups: (1) patients without IAI who had received antenatal corticosteroids (n = 21), (2) patients with IAI who had received antenatal corticosteroids (n = 9), (3) patients without IAI who had not received antenatal corticosteroids (n = 11), and (4) patients with IAI who had not received antenatal corticosteroids (n = 7). Amniotic fluid was obtained by transabdominal amniocentesis. SP-A, SP-B, and SP-D concentrations in amniotic fluid were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric statistics were used for analysis. RESULTS: Women with IAI had a higher median amniotic fluid concentration of SP-B and of SP-B/total protein, but not other SPs, than those without IAI (both p = 0.03). Among patients who had received antenatal corticosteroids, the median amniotic fluid concentration of SP-B and of SP-B/total protein was significantly higher in patients with IAI than in those without IAI (SP-B, IAI: median 148 ng/mL, range 37.3-809 ng/mL vs. without IAI: median 7.2 ng/mL, range 0-1035 ng/mL; p = 0.005 and SP-B/total protein, IAI: median 14.1 ng/mg, range 4.3-237.5 ng/mg vs. without IAI: median 1.45 ng/mg, range 0-79.5 ng/mg; p = 0.003). Among women who had not received antenatal corticosteroids, the median amniotic fluid concentrations of SP-B and of SP-B/total protein were not significantly different between patients with and without IAI (SP-B, IAI: median 4 ng/mL, range 0-31.4 ng/mL vs. without IAI: median 3.4 ng/mL, range 0-37 ng/mL; p = 0.8 and SP-B/total protein, IAI: median 0.55 ng/mg, range 0-6.96 ng/mg vs. without IAI: median 0.59 ng/mg, range 0-3.28 ng/mg; p = 0.9). The median amniotic fluid concentrations of SP-A, SP-A/total protein, SP-D, and SP-D/total protein were not significantly different between patients with and without IAI whether they received antenatal corticosteroids or not (all p > 0.05). CONCLUSIONS: IAI was associated with an increased amniotic fluid concentration of SP-B in patients who received antenatal corticosteroids within 7 days prior to amniocentesis.