scholarly journals Examination of Surfactant Protein D as a Biomarker for Evaluating Pulmonary Toxicity of Nanomaterials in Rat

2021 ◽  
Vol 22 (9) ◽  
pp. 4635
Author(s):  
Taisuke Tomonaga ◽  
Hiroto Izumi ◽  
Yukiko Yoshiura ◽  
Chinatsu Nishida ◽  
Kazuhiro Yatera ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Pulmonary Toxicity ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Operating Characteristics ◽  
Low Toxicity ◽  
Titanium Dioxides ◽  
The Relationship

This work studies the relationship between lung inflammation caused by nanomaterials and surfactant protein D (SP-D) kinetics and investigates whether SP-D can be a biomarker of the pulmonary toxicity of nanomaterials. Nanomaterials of nickel oxide and cerium dioxide were classified as having high toxicity, nanomaterials of two types of titanium dioxides and zinc oxide were classified as having low toxicity, and rat biological samples obtained from 3 days to 6 months after intratracheal instillation of those nanomaterials and micron-particles of crystalline silica were used. There were different tendencies of increase between the high- and low-toxicity materials in the concentration of SP-D in bronchoalveolar-lavage fluid (BALF) and serum and in the expression of the SP-D gene in the lung tissue. An analysis of the receiver operating characteristics for the toxicity of the nanomaterials by SP-D in BALF and serum showed a high accuracy of discrimination from 1 week to 3 or 6 months after exposure. These data suggest that the differences in the expression of SP-D in BALF and serum depended on the level of lung inflammation caused by the nanomaterials and that SP-D can be biomarkers for evaluating the pulmonary toxicity of nanomaterials.

scholarly journals Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1563
Author(s):  
Taisuke Tomonaga ◽  
Hiroto Izumi ◽  
Takako Oyabu ◽  
Byeong-Woo Lee ◽  
Masaru Kubo ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Inhalation Exposure ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
High Toxicity ◽  
Operating Characteristics ◽  
Low Toxicity ◽  
Titanium Dioxides ◽  
Dose Dependent

This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after intratracheal instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following intratracheal instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both intratracheal instillation and inhalation exposure.

Complement-mediated host defense in the lung

2000 ◽  
Vol 279 (5) ◽  
pp. L790-L798 ◽  
Author(s):  
Wendy T. Watford ◽  
Andrew J. Ghio ◽  
Jo Rae Wright
Keyword(s):  
Alternative Pathway ◽  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
The Body ◽  
Surfactant Protein D ◽  
Classical Pathway ◽  
Pathway Activity ◽  
Protein Factor ◽  
Pathway Activation

Complement is a system of plasma proteins that aids in the elimination of pathogens from the body. We hypothesized that there is a functional complement system present in the lung that aids in the removal of pathogens. Western blot analysis revealed complement proteins of the alternative and classical pathways of complement in bronchoalveolar lavage fluids (BALF) from healthy volunteers. Functional classical pathway activity was detected in human BALF, but there was no significant alternative pathway activity in lavage fluid, a finding that correlates with the low level of the alternative pathway protein, factor B, in these samples. Although the classical pathway of complement was functional in lavage fluid, the level of the classical pathway activator C1q was very low. We tested the ability of the lung- specific surfactant proteins, surfactant protein A (SP-A) and surfactant protein D (SP-D), to substitute for C1q in classical pathway activation, since they have structural homology to C1q. However, neither SP-A nor SP-D restored classical pathway activity to C1q-depleted serum. These data suggest that the classical pathway of complement is functionally active in the lung where it may play a role in the recognition and clearance of bacteria.

scholarly journals Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity

2000 ◽  
Vol 351 (2) ◽  
pp. 449-458 ◽  
Author(s):  
Kevan L. HARTSHORN ◽  
Mitchell R. WHITE ◽  
Dennis R. VOELKER ◽  
John COBURN ◽  
Ken ZANER ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Surfactant Protein ◽  
Systematic Evaluation ◽  
Surfactant Protein D ◽  
Globular Domain ◽  
Influenza A Viruses ◽  
Viral Neutralization ◽  
The Relationship ◽  
Haemagglutination Activity

Collectins are important in the initial containment of a variety of pathogens, including influenza A virus (IAV). We provide the first systematic evaluation of the oligosaccharide-binding sites for pulmonary surfactant protein D (SP-D) on specific IAV coat glycoproteins and define the relationship between this binding and antiviral activity. With the use of several techniques, SP-D was found to bind via its carbohydrate-recognition domain (CRD) to mannosylated, N-linked carbohydrates on the HA1 domain of the haemagglutinin (HA) and on the neuraminidase of IAV. Using a set of IAV strains that differed in the level and site of glycosylation, and a panel of recombinant collectins, we found that binding of SP-D to the globular domain of the HA was critical in mediating the inhibition of viral haemagglutination activity and infectivity. We also demonstrated that the pattern of binding of a collectin to IAV glycoproteins can be modified by altering the monosaccharide-binding affinity of its CRD or by linking the CRD to a different N-terminal/collagen domain. These studies clarify the mechanisms of viral neutralization by collectins and might be useful in engineering collectins for enhanced antiviral activity.

scholarly journals Surfactant protein D and bronchopulmonary dysplasia: a new way to approach an old problem

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Raquel Arroyo ◽  
Paul S. Kingma
Keyword(s):  
Immune Response ◽  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Tissue Injury ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Innate Immune ◽  
Surfactant Protein D

AbstractSurfactant protein D (SP-D) is a collectin protein synthesized by alveolar type II cells in the lungs. SP-D participates in the innate immune defense of the lungs by helping to clear infectious pathogens and modulating the immune response. SP-D has shown an anti-inflammatory role by down-regulating the release of pro-inflammatory mediators in different signaling pathways such as the TLR4, decreasing the recruitment of inflammatory cells to the lung, and modulating the oxidative metabolism in the lungs. Recombinant human SP-D (rhSP-D) has been successfully produced mimicking the structure and functions of native SP-D. Several in vitro and in vivo experiments using different animal models have shown that treatment with rhSP-D reduces the lung inflammation originated by different insults, and that rhSP-D could be a potential treatment for bronchopulmonary dysplasia (BPD), a rare disease for which there is no effective therapy up to date. BPD is a complex disease in preterm infants whose incidence increases with decreasing gestational age at birth. Lung inflammation, which is caused by different prenatal and postnatal factors like infections, lung hyperoxia and mechanical ventilation, among others, is the key player in BPD. Exacerbated inflammation causes lung tissue injury that results in a deficient gas exchange in the lungs of preterm infants and frequently leads to long-term chronic lung dysfunction during childhood and adulthood. In addition, low SP-D levels and activity in the first days of life in preterm infants have been correlated with a worse pulmonary outcome in BPD. Thus, SP-D mediated functions in the innate immune response could be critical aspects of the pathogenesis in BPD and SP-D could inhibit lung tissue injury in this preterm population. Therefore, administration of rhSP-D has been proposed as promising therapy that could prevent BPD.

scholarly journals Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials

2021 ◽  
Vol 11 (24) ◽  
pp. 11990
Author(s):  
Yng-Tay Chen ◽  
Po-Yi Lue ◽  
Po-Wei Chen ◽  
Pin-Ju Chueh ◽  
Fuu-Jen Tsai ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Solid Content ◽  
Inhalation Toxicity ◽  
Nano Sio2 ◽  
Negative Results ◽  
Significant Difference ◽  
Chromosomal Aberration Test ◽  
Surface Modified

Surface-modified nano-SiO2 is a common additive in many products. However, the safety of nano-SiO2 products under various modifications is still unclear. In this study, we investigated the genotoxicity and acute pulmonary toxicity of nano-SiO2 with or without modification. The samples used in this study included: sample A (SA, 55.16 nm, 411.3 mg/mL), modified sample A (mSA, 82.29 nm, 37.7 mg/mL), sample B (SB, 22 nm, 358.0 mg/mL), and modified sample B (mSB, 86.64 nm, 37.7 mg/mL). In the genotoxicity study, we conducted an Ames test, chromosomal aberration test (CA), and a micronucleus (MN) test. The SA, mSA, and mSB groups showed negative results in all these genotoxicity tests. Only SB showed a weakly positive reaction in these assays, but the genotoxicity could be reversed after S9 metabolism or modification. In the acute pulmonary toxicity test, the rats were given an intratracheal instillation (IT) (0.5 mL/kg) of diluted samples and sacrificed after 1 or 14 days. The mortality rate, number of leukocytes and cytokines of TNF-α in the bronchoalveolar lavage fluid (BALF), and the pathology in the lungs were determined. The results revealed that mSA posed acute toxicity in rats. After modification, the pulmonary toxicity was increased in mSA but decreased in mSB on Day 1, and no significant difference was observed on Day 14. In conclusion, there was no observed genotoxicity in either SA or SB, while mSA posed acute inhalation toxicity to rats that decreased in mSB after modification. This indicates that the decrease in pH level in SA and decrease in the solid content in SB are considered after the trifluorosilane surface-modified amorphous nano-silica.

Surfactant protein D enhancesPneumocystisinfection in immune-suppressed mice

2006 ◽  
Vol 290 (3) ◽  
pp. L442-L449 ◽  
Author(s):  
Zvezdana Vuk-Pavlović ◽  
Eun K. Mo ◽  
Crystal R. Icenhour ◽  
Joseph E. Standing ◽  
James H. Fisher ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Pneumocystis Pneumonia ◽  
Eosinophil Infiltration ◽  
Surfactant Protein D ◽  
Infection Period ◽  
Inflammatory Parameters ◽  
Inflammatory Protein ◽  
And Function

To further determine the role of surfactant protein (SP)-D in the pathogenesis of Pneumocystis pneumonia, a mouse model of transgenic overexpression (OE) of SP-D was studied. These animals produce roughly 30- to 50-fold greater SP-D than their wild-type (WT) counterparts but show no other differences in lung morphology and function. Animals in both the SP-D OE and WT groups were depleted of CD4 lymphocytes with weekly injections of GK1.5 antibody, before Pneumocystis inoculation, and throughout the subsequent infection period. At various time points, mice were killed and analyzed for inflammatory parameters and organism burden. Proinflammatory cytokines in bronchoalveolar lavage fluid were elevated throughout the period of infection, with OE animals exhibiting significantly higher levels of TNF-α and macrophage inflammatory protein-2 compared with WT controls. The total number of cells in the lavage fluid was also increased significantly only in the OE group, whereas the cell differential composition demonstrated lymphocyte and eosinophil infiltration in both groups of animals. Significantly, the organism burden was markedly higher in the SP-D OE animals, whereas the WT mice demonstrated little alteration in organism number over the course of infection. These results further indicate that SP-D facilitates the development of Pneumocystis infection and related lung inflammation in an immunosuppressed mouse model.

Human salivary agglutinin binds to lung surfactant protein-D and is identical with scavenger receptor protein gp-340

2001 ◽  
Vol 359 (1) ◽  
pp. 243-248 ◽  
Author(s):  
Toon J. M. LIGTENBERG ◽  
Floris J. BIKKER ◽  
Jasper GROENINK ◽  
Ida TORNOE ◽  
Rikke LETH-LARSEN ◽  
...  
Keyword(s):  
Mass Spectrum ◽  
Lung Surfactant ◽  
Scavenger Receptor ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Tumour Suppressor Gene ◽  
Receptor Protein ◽  
Surfactant Protein D ◽  
Oral Streptococci ◽  
Lung Surfactant Protein

Salivary agglutinin is a 300–400kDa salivary glycoprotein that binds to antigen B polypeptides of oral streptococci, thereby playing a role in their colonization and the development of caries. A mass spectrum was recorded of a trypsin digest of agglutinin. A dominant peak of 1460Da was sequenced by quadrupole time-of-flight (Q-TOF) tandem MS. The sequence showed 100% identity with part of the scavenger receptor cysteine-rich (‘SRCR’) domain found in gp-340/DMBT1 (deleted in malignant brain tumours-1). The mass spectrum revealed 11 peaks with an identical mass as a computer-simulated trypsin digest of gp-340. gp-340 is a 340kDa glycoprotein isolated from bronchoalveolar lavage fluid that binds specifically to lung surfactant protein-D. DMBT1 is a candidate tumour suppressor gene. A search in the human genome revealed only one copy of this gene. The molecular mass, as judged from SDS/PAGE and the amino acid composition of agglutinin, was found to be nearly identical with that of gp-340. It was shown by Western blotting that monoclonal antibodies against gp-340 reacted with salivary agglutinin, and monoclonals against agglutinin reacted with gp-340. It was demonstrated that gp-340 and agglutinin bound in a similar way to Streptococcus mutans and surfactant protein-D. Histochemically, the distribution of gp-340 in the submandibular salivary glands was identical with the agglutinin distribution, as shown in a previous paper [Takano, Bogert, Malamud, Lally and Hand (1991) Anat. Rec. 230, 307–318]. We conclude that agglutinin is identical with gp-340, and that this molecule interacts with S. mutans and surfactant protein-D.

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