scholarly journals Impact of Surfactant Protein-A Variants on Survival in Aged Mice in Response to Klebsiella pneumoniae Infection and Ozone: Serendipity in Action

2020 ◽  
Vol 8 (9) ◽  
pp. 1276
Author(s):  
Nithyananda Thorenoor ◽  
David S. Phelps ◽  
Padma Kala ◽  
Radhika Ravi ◽  
Andreas Floros Phelps ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Application ◽  
Protein A ◽  
Surfactant Protein ◽  
Innate Immune ◽  
Young Mouse ◽  
Surfactant Protein A ◽  
Aged Mice ◽  
Significant Magnitude ◽  
The Impact

Innate immune molecules, SP-A1 (6A2, 6A4) and SP-A2 (1A0, 1A3), differentially affect young mouse survival after infection. Here, we investigated the impact of SP-A variants on the survival of aged mice. hTG mice carried a different SP-A1 or SP-A2 variant and SP-A-KO were either infected with Klebsiella pneumoniae or exposed to filtered air (FA) or ozone (O3) prior to infection, and their survival monitored over 14 days. In response to infection alone, no gene- or sex-specific (except for 6A2) differences were observed; variant-specific survival was observed (1A0 > 6A4). In response to O3, gene-, sex-, and variant-specific survival was observed with SP-A2 variants showing better survival in males than females, and 1A0 females > 1A3 females. A serendipitous, and perhaps clinically important observation was made; mice exposed to FA prior to infection exhibited significantly better survival than infected alone mice. 1A0 provided an overall better survival in males and/or females indicating a differential role for SP-A genetics. Improved ventilation, as provided by FA, resulted in a survival of significant magnitude in aged mice and perhaps to a lesser extent in young mice. This may have clinical application especially within the context of the current pandemic.

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 Impact of Ozone, Sex, and Gonadal Hormones on Bronchoalveolar Lavage Characteristics and Survival in SP-A KO Mice Infected with Klebsiella pneumoniae

2020 ◽  
Vol 8 (9) ◽  
pp. 1354
Author(s):  
Chintan K. Gandhi ◽  
Anatoly N. Mikerov ◽  
Faryal Durrani ◽  
Todd M. Umstead ◽  
Sanmei Hu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bronchoalveolar Lavage ◽  
Tissue Damage ◽  
Protein A ◽  
Surfactant Protein ◽  
Gonadal Hormones ◽  
Minimal Impact ◽  
Markers Of Inflammation ◽  
Inflammatory Protein ◽  
The Impact

Surfactant protein A (SP-A) plays an important role in innate immunity. The sex-dependent survival of infected SP-A knockout (KO) mice has been observed. Our goal was to study the impact of ozone (O3) and sex, as well as gonadal hormones, on the bronchoalveolar lavage (BAL) readouts and survival, respectively, of Klebsiella pneumoniae-infected SP-A KO mice. Male and female SP-A KO mice were exposed to O3 or filtered air and infected with K. pneumoniae. We studied markers of inflammation and tissue damage at 4, 24, and 48 h, as well as the survival over 14 days, of gonadectomized (Gx) mice implanted with control pellets (CoP) or hormone (5α-dihydrotestosterone (DHT) in female gonadectomized mice (GxF) or 17β-estradiol (E2) in male gonadectomized mice (GxM)). We observed: (1) an increase in neutrophil and macrophage inflammatory protein-2 levels as time progressed post-infection, and O3 exposure appeared to increase this response; (2) an increase in lactate dehydrogenase, total protein, oxidized protein, and phospholipids in response to O3 with no consistent sex differences in studied parameters; and (3) a reduction in survival of the GxM and CoP mice, the GxM and E2 mice, and the GxF and DHT mice but not for the GxF and CoP mice after O3. Without SP-A, (a) sex was found to have a minimal impact on BAL cellular composition and tissue damage markers, and (b) the impact of gonadal hormones on survival was found to involve different mechanisms than in the presence of SP-A.

scholarly journals Respiratory syncytial virus infection alters surfactant protein A expression in human pulmonary epithelial cells by reducing translation efficiency

2009 ◽  
Vol 297 (4) ◽  
pp. L559-L567 ◽  
Author(s):  
Shirley R. Bruce ◽  
Constance L. Atkins ◽  
Giuseppe N. Colasurdo ◽  
Joseph L. Alcorn
Keyword(s):  
Steady State ◽  
Protein A ◽  
Surfactant Protein ◽  
Innate Immune ◽  
Surfactant Protein A ◽  
Translation Efficiency ◽  
Type Ii ◽  
Protein Levels ◽  
Rsv Infection ◽  
Syncytial Virus

Infection of neonatal lung by respiratory syncytial virus (RSV) is a common cause of respiratory dysfunction. Lung alveolar type II and bronchiolar epithelial (Clara) cells secrete surfactant protein A (SP-A), a collectin that is an important component of the pulmonary innate immune system. SP-A binds to the virus, targeting the infectious agent for clearance by host defense mechanisms. We have previously shown that while the steady-state level of SP-A mRNA increases approximately threefold after RSV infection, steady-state levels of cellular and secreted SP-A protein decrease 40–60% in human type II cells in primary culture, suggesting a mechanism where the virus alters components of the innate immune response in infected cells. In these studies, we find that changes in SP-A mRNA and protein levels in RSV-infected NCI-H441 cells (a bronchiolar epithelial cell line) recapitulate the results in SP-A expression observed in primary lung cells. While SP-A protein is normally ubiquitinated, there is no change in the level of SP-A protein ubiquitination or proteasome activity during RSV infection, suggesting that the reduced levels of SP-A protein are not due to degradation by activated proteasomes. SP-A mRNA is appropriately processed and exported from the nucleus to the cytoplasm during RSV infection. As evidenced by polysome analysis of SP-A mRNA and pulse-chase analysis of newly synthesized SP-A protein, we find a decrease in translational efficiency that is specific for SP-A mRNA. Therefore, the decrease in SP-A protein levels observed after RSV infection of pulmonary bronchiolar epithelial cells results from a mechanism that affects SP-A mRNA translation efficiency.

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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