scholarly journals Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 915
Author(s):  
He N. Xu ◽  
Zhenwu Lin ◽  
Chintan K. Gandhi ◽  
Shaili Amatya ◽  
Yunhua Wang ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Imaging Technique ◽  
Redox Balance ◽  
Surfactant Protein ◽  
Redox Status ◽  
Innate Immune ◽  
Ozone Exposure ◽  
Dependent Manner ◽  
Immune Molecule ◽  
Air Control

Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner. We investigated the NAD(H) redox status of AM from SP-A2 and SP-A knockout (KO) mice in response to O3 or filtered air (control) exposure using optical redox imaging technique. We found: (i) In SP-A2 mice, the redox alteration of AM in response to O3 showed sex-dependence with AM from males being significantly more oxidized and having a higher level of mitochondrial reactive oxygen species than females; (ii) AM from KO mice were more oxidized after O3 exposure and showed no sex differences; (iii) AM from female KO mice were more oxidized than female SP-A2 mice; and (iv) Two distinct subpopulations characterized by size and redox status were observed in a mouse AM sample. In conclusions, the NAD(H) redox balance in AM responds to O3 in a sex-dependent manner and the innate immune molecule, SP-A2, contributes to this observed sex-specific redox response.

scholarly journals The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 784 ◽  
Author(s):  
Fotios Tekos ◽  
Zoi Skaperda ◽  
Nikolaos Goutzourelas ◽  
David S. Phelps ◽  
Joanna Floros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein A ◽  
The Elderly ◽  
Redox Balance ◽  
Surfactant Protein ◽  
Redox Status ◽  
Innate Immune ◽  
Differential Outcomes ◽  
Underlying Diseases ◽  
And Oxidative Stress

The pandemic of COVID-19 is of great concern to the scientific community. This mainly affects the elderly and people with underlying diseases. People with obesity are more likely to experience unpleasant disease symptoms and increased mortality. The severe oxidative environment that occurs in obesity due to chronic inflammation permits viral activation of further inflammation leading to severe lung disease. Lifestyle affects the levels of inflammation and oxidative stress. It has been shown that a careful diet rich in antioxidants, regular exercise, and fasting regimens, each and/or together, can reduce the levels of inflammation and oxidative stress and strengthen the immune system as they lead to weight loss and activate cellular antioxidant mechanisms and reduce oxidative damage. Thus, a lifestyle change based on the three pillars: antioxidants, exercise, and fasting could act as a proactive preventative measure against the adverse effects of COVID-19 by maintaining redox balance and well-functioning immunity. Moreover, because of the observed diversity in the expression of COVID-19 inflammation, the role of genetics of innate immune molecules, surfactant protein A (SP-A)1 and SP-A2, and their differential impact on the local lung microenvironment and host defense is reviewed as genetics may play a major role in the diverse expression of the disease.

scholarly journals Impact of ozone exposure on the phagocytic activity of human surfactant protein A (SP-A) and SP-A variants

2008 ◽  
Vol 294 (1) ◽  
pp. L121-L130 ◽  
Author(s):  
Anatoly N. Mikerov ◽  
Todd M. Umstead ◽  
Xiaozhuang Gan ◽  
Weixiong Huang ◽  
Xiaoxuan Guo ◽  
...  
Keyword(s):  
Phagocytic Activity ◽  
Protein A ◽  
Surfactant Protein ◽  
Redox Status ◽  
Ozone Exposure ◽  
Surfactant Protein A ◽  
Phagocytic Index ◽  
Dependent Manner

Surfactant protein A (SP-A) enhances phagocytosis of Pseudomonas aeruginosa. SP-A1 and SP-A2 encode human (h) SP-A; SP-A2 products enhance phagocytosis more than SP-A1. Oxidation can affect SP-A function. We hypothesized that in vivo and in vitro ozone-induced oxidation of SP-A (as assessed by its carbonylation level) negatively affects its function in phagocytosis (as assessed by bacteria cell association). To test this, we used P. aeruginosa, rat alveolar macrophages (AMs), hSP-As with varying levels of in vivo (natural) oxidation, and ozone-exposed SP-A2 (1A, 1A0) and SP-A1 (6A2, 6A4) variants. SP-A oxidation levels (carbonylation) were measured; AMs were incubated with bacteria in the presence of SP-A, and the phagocytic index was calculated. We found: 1) the phagocytic activity of hSP-A is reduced with increasing levels of in vivo SP-A carbonylation; 2) in vitro ozone exposure of hSP-A decreases its function in a dose-dependent manner as well as its ability to enhance phagocytosis of either gram-negative or gram-positive bacteria; 3) the activity of both SP-A1 and SP-A2 decreases in response to in vitro ozone exposure of proteins with SP-A2 being affected more than SP-A1. We conclude that both in vivo and in vitro oxidative modifications of SP-A by carbonylation reduce its ability to enhance phagocytosis of bacteria and that the activity of SP-A2 is affected more by in vitro ozone-induced oxidation. We speculate that functional differences between SP-A1 and SP-A2 exist in vivo and that the redox status of the lung microenvironment differentially affects function of SP-A1 and SP-A2.

scholarly journals Expression of Surfactant Protein D in the Human Gastric Mucosa and during Helicobacter pylori Infection

2002 ◽  
Vol 70 (3) ◽  
pp. 1481-1487 ◽  
Author(s):  
Emma Murray ◽  
Wafa Khamri ◽  
Marjorie M. Walker ◽  
Paul Eggleton ◽  
Anthony P. Moran ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Surfactant Protein ◽  
Normal Mucosa ◽  
Innate Immune ◽  
Surfactant Protein D ◽  
Human Gastric Mucosa ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Immune Molecule ◽  
H Pylori

ABSTRACT Helicobacter pylori establishes persistent infection of gastric mucosa with diverse clinical outcomes. The innate immune molecule surfactant protein D (SP-D) binds selectively to microorganisms, inducing aggregation and phagocytosis. In this study, we demonstrated the expression of SP-D in gastric mucosa by reverse transcription-PCR and immuohistochemical analysis. SP-D is present at the luminal surface and within the gastric pits, with maximal expression at the surface. Levels of expression are significantly increased in H. pylori-associated gastritis compared to those in the normal mucosa. Immunofluorescence microscopy was used to demonstrate binding and agglutination of H. pylori by SP-D in a lectin-specific manner. These activities resulted in a 50% reduction in the motility of H. pylori, as judged on the basis of curvilinear velocity measured by using a Hobson BacTracker. Lipopolysaccharides extracted from three H. pylori strains were shown to bind SP-D in a concentration-dependent manner, and there was marked variation in the avidity of binding among the strains. SP-D may therefore play a significant role in the innate immune response to H. pylori infection.

scholarly journals Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophages ◽  
Redox State ◽  
Redox Status ◽  
Nutrient Starvation ◽  
Ozone Exposure ◽  
Reduced Form ◽  
Time Period ◽  
Lag Times ◽  
The Impact

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

scholarly journals Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages

1992 ◽  
Vol 286 (1) ◽  
pp. 5-8 ◽  
Author(s):  
J F Van Iwaarden ◽  
H Shimizu ◽  
P H M Van Golde ◽  
D R Voelker ◽  
L M G Van Golde
Keyword(s):  
Alveolar Macrophages ◽  
Oxygen Radicals ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Surfactant Protein D ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Oxygen Radical Production ◽  
Stimulation Of

Rat surfactant protein D (SP-D) was shown to enhance the production of oxygen radicals by rat alveolar macrophages. This enhancement, which was determined by a lucigenin-dependent chemiluminescence assay, was maximal after 18 min at an SP-D concentration of 0.2 micrograms/ml. Surfactant lipids did not influence the stimulation of alveolar macrophages by SP-D, whereas the oxygen-radical production of these cells induced by surfactant protein A was inhibited by the lipids in a concentration-dependent manner.

SP-A1 and SP-A2 variants differentially enhance association ofPseudomonas aeruginosawith rat alveolar macrophages

2005 ◽  
Vol 288 (1) ◽  
pp. L150-L158 ◽  
Author(s):  
Anatoly N. Mikerov ◽  
Todd M. Umstead ◽  
Weixiong Huang ◽  
Wenlei Liu ◽  
David S. Phelps ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Single Gene ◽  
Protein A ◽  
Surfactant Protein ◽  
Phagocytic Index ◽  
Dependent Manner ◽  
Gene Products ◽  
Concentration Dependent Manner ◽  
Cell Association

Chronic airway inflammation caused by Pseudomonas aeruginosa is an important feature of cystic fibrosis (CF). Surfactant protein A (SP-A) enhances phagocytosis of P. aeruginosa. Two genes, SP-A1 and SP-A2, encode human SP-A. We hypothesized that genetically determined differences in the activity of SP-A1 and SP-A2 gene products exist. To test this, we studied association of a nonmucoid P. aeruginosa strain (ATCC 39018) with rat alveolar macrophages in the presence or absence of insect cell-expressed human SP-A variants. We used two trios, each consisting of SP-A1, SP-A2, and their coexpressed SP-A1/SP-A2 variants. We tested the 6A2and 6A4alleles (for SP-A1), the 1A0and 1A alleles (for SP-A2), and their respective coexpressed SP-A1/SP-A2 gene products. After incubation of alveolar macrophages with P. aeruginosa in the presence of the SP-A variants at 37°C for 1 h, the cell association of bacteria was assessed by light microscopy analysis. We found 1) depending on SP-A concentration and variant, SP-A2 variants significantly increased the cell association more than the SP-A1 variants (the phagocytic index for SP-A1 was ∼52–95% of the SP-A2 activity); 2) coexpressed variants at certain concentrations were more active than single gene products; and 3) the phagocytic index for SP-A variants was ∼18–41% of the human SP-A from bronchoalveolar lavage. We conclude that human SP-A variants in vitro enhance association of P. aeruginosa with rat alveolar macrophages differentially and in a concentration-dependent manner, with SP-A2 variants having a higher activity compared with SP-A1 variants.

scholarly journals Surfactant protein A enhances the phagocytosis of C1q-coated particles by alveolar macrophages

2002 ◽  
Vol 283 (5) ◽  
pp. L1011-L1022 ◽  
Author(s):  
Wendy T. Watford ◽  
Molly B. Smithers ◽  
Michael M. Frank ◽  
Jo Rae Wright
Keyword(s):  
Alveolar Macrophages ◽  
Solid Phase ◽  
Protein A ◽  
Surfactant Protein ◽  
Protective Role ◽  
Innate Immune ◽  
Multiple Roles ◽  
Surfactant Protein A ◽  
Complement Protein ◽  
Functional Consequences

Surfactant protein-A (SP-A) plays multiple roles in pulmonary host defense, including stimulating bacterial phagocytosis by innate immune cells. Previously, SP-A was shown to interact with complement protein C1q. Our goal was to further characterize this interaction and elucidate its functional consequences. Radiolabeled SP-A bound solid-phase C1q but not other complement proteins tested. The lectin activity of SP-A was not required for binding to C1q. Because C1q is involved in bacterial clearance but alone does not efficiently enhance the phagocytosis of most bacteria, we hypothesize that SP-A enhances phagocytosis of C1q-coated antigens. SP-A enhanced by sixfold the percentage of rat alveolar macrophages in suspension that phagocytosed C1q-coated fluorescent beads. Furthermore, uptake of C1q-coated beads was enhanced when either beads or alveolar macrophages were preincubated with SP-A. In contrast, SP-A had no significant effect on the uptake of C1q-coated beads by alveolar macrophages adhered to plastic slides. We conclude that SP-A may serve a protective role in the lung by interacting with C1q to enhance the clearance of foreign particles.

scholarly journals Cellular Response to Trypanosoma cruzi Infection Induces Secretion of Defensin α-1, Which Damages the Flagellum, Neutralizes Trypanosome Motility, and Inhibits Infection

2013 ◽  
Vol 81 (11) ◽  
pp. 4139-4148 ◽  
Author(s):  
Candice A. Johnson ◽  
Girish Rachakonda ◽  
Yuliya Y. Kleshchenko ◽  
Pius N. Nde ◽  
M. Nia Madison ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Innate Immune ◽  
Short Exposure ◽  
Dependent Manner ◽  
Content Type ◽  
Human Parasite ◽  
Immune Molecule ◽  
Flagellar Membrane ◽  
Parasite Motility ◽  
Hct116 Cells

ABSTRACTHuman defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that colonic epithelial model HCT116 cells respond toTrypanosoma cruziinfection by secreting defensin α-1, which reduces infection. We also report the early effects of defensin α-1 on invasive trypomastigotes that involve damage of the flagellar structure to inhibit parasite motility and reduce cellular infection. Short exposure of defensin α-1 to trypomastigotes shows that defensin α-1 binds to the flagellum, resulting in flagellar membrane and axoneme alterations, followed by breaking of the flagellar membrane connected to the trypanosome body, leading to detachment and release of the parasite flagellum. In addition, defensin α-1 induces a significant reduction in parasite motility in a peptide concentration-dependent manner, which is abrogated by anti-defensin α-1 IgG. Preincubation of trypomastigotes with a concentration of defensin α-1 that inhibits 50% trypanosome motility significantly reduced cellular infection by 80%. Thus, human defensin α-1 is an innate immune molecule that is secreted by HCT116 cells in response toT. cruziinfection, inhibitsT. cruzimotility, and plays an important role in reducing cellular infection. This is the first report showing a novel cellular innate immune response to a human parasite by secretion of defensin α-1, which neutralizes the motility of a human parasite to reduce cellular infection. The mode of activity of human defensin α-1 againstT. cruziand its function may provide insights for the development of new antiparasitic strategies.

Surfactant protein A modulates the differentiation of murine bone marrow-derived dendritic cells

2003 ◽  
Vol 284 (1) ◽  
pp. L232-L241 ◽  
Author(s):  
Karen G. Brinker ◽  
Hollie Garner ◽  
Jo Rae Wright
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Adaptive Immunity ◽  
Protein A ◽  
Surfactant Protein ◽  
Innate Immune ◽  
Surfactant Protein A ◽  
Immune Functions ◽  
Murine Bone Marrow ◽  
Immune Molecule

Surfactant protein A (SP-A) is an innate immune molecule that regulates pathogen clearance and lung inflammation. SP-A modulates innate immune functions such as phagocytosis, cytokine production, and chemotaxis; however, little is known about regulation of adaptive immunity by SP-A. Dendritic cells (DCs) are the most potent antigen-presenting cell with the unique capacity to activate naı̈ve T cells and initiate adaptive immunity. The goal of this study was to test the hypothesis that SP-A regulates the differentiation of immature DCs into potent T cell stimulators. The data show that incubation of immature DCs for 24 h with SP-A inhibits basal- and LPS-mediated expression of major histocompatibility complex class II and CD86. Stimulation of immature DCs by SP-A also inhibits the allostimulation of T cells, enhances dextran endocytosis, and alters DC chemotaxis toward RANTES and secondary lymphoid tissue chemokine. The effects on DC phenotype and function are similar for the structurally homologous C1q, but not for SP-D. These studies demonstrate that SP-A participates in the adaptive immune response by modulating important immune functions of DCs.

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