<i>P. carinii</i>induces selective alterations in component expression and biophysical activity of lung surfactant

Atochina, Elena N.; Beers, Michael F.; Scanlon, Seth Thomas; Preston, Angela M.; Beck, James M.

doi:10.1152/ajplung.2000.278.3.l599

Cited by 62 publications

(73 citation statements)

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“…This study demonstrates that allergen exposure increased production of the im- Although inflammatory changes of the lung generally induce enhanced expression of both collectins (SP-A and SP-D) (42,43), allergic inflammation appeared to result in an intriguing selective increase of SP-D protein levels in our previous studies (24,25). SP-D expression is known to be induced by hormones and second messengers including dexamethasone, insulin, cAMP, and phorbol ester (44,45) but cytokines that are central for development of a Th2-type inflammatory response have also been implicated.…”

Section: Discussionmentioning

confidence: 65%

IL-4 and IL-13 Form a Negative Feedback Circuit with Surfactant Protein-D in the Allergic Airway Response

Haczku

Cao

Vass

et al. 2006

The Journal of Immunology

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127

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The innate immune molecule surfactant protein-D (SP-D) plays an important regulatory role in the allergic airway response. In this study, we demonstrate that mice sensitized and challenged with either Aspergillus fumigatus (Af) or OVA have increased SP-D levels in their lung. SP-D mRNA and protein levels in the lung also increased in response to either rIL-4 or rIL-13 treatment. Type II alveolar epithelial cell expression of IL-4Rs in mice sensitized and challenged with Af, and in vitro induction of SP-D mRNA and protein by IL-4 and IL-13, but not IFN-γ, suggested a direct role of IL-4R-mediated events. The regulatory function of IL-4 and IL-13 was further supported in STAT-6-deficient mice as well as in IL-4/IL-13 double knockout mice that failed to increase SP-D production upon allergen challenge. Interestingly, addition of rSP-D significantly inhibited Af-driven Th2 cell activation in vitro whereas mice lacking SP-D had increased numbers of CD4+ cells with elevated IL-13 and thymus- and activation-regulated chemokine levels in the lung and showed exaggerated production of IgE and IgG1 following allergic sensitization. We propose that allergen exposure induces elevation in SP-D protein levels in an IL-4/IL-13-dependent manner, which in turn, prevents further activation of sensitized T cells. This negative feedback regulatory circuit could be essential in protecting the airways from inflammatory damage after allergen inhalation.

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Section: Discussionmentioning

confidence: 65%

IL-4 and IL-13 Form a Negative Feedback Circuit with Surfactant Protein-D in the Allergic Airway Response

Haczku

Cao

Vass

et al. 2006

The Journal of Immunology

Self Cite

127

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“…The percentage of large aggregates and their content of SP-A and SP-B are reduced in bronchoalveolar lavage from patients with ARDS [38][39][40]. Animal studies of ALI/ARDS indicate that large surfactant aggregates can be depleted or reduced in activity by molecular interactions with inhibitor substances as well as by changes in surfactant aggregate metabolism in the alveoli or involving altered reuptake or recycling in type II cells [30,60,[79][80][81]. Although large aggregates are depleted or compromised in many forms of ALI/ARDS, information on total surfactant pools is inconsistent, with both decreased [35,37] and unchanged amounts [34,36] reported.…”

Section: Surfactant Dysfunction In Acute Pulmonary Injurymentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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“…These collectins are implicated in the attachment of Pneumocystis to alveolar epithelial cells during infection (4 -6) and evasion of the host immune response (7). In contrast, surfactant proteins B (8) and C (4,9) are down-regulated in their expression. Macrophage mannose receptor expression is also down-regulated (10), although the shed form of the mannose receptor is increased (11), which may help the organism evade host immune responses (7,10,11).…”

mentioning

confidence: 91%

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

Lasbury

Merali

Durant

et al. 2007

Journal of Biological Chemistry

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The number of alveolar macrophages is decreased during Pneumocystis pneumonia (Pcp), partly because of activation of apoptosis in these cells. This apoptosis occurs in both rat and mouse models of Pcp. Bronchoalveolar lavage (BAL) fluids from Pneumocystis-infected animals were found to contain high levels of polyamines, including spermidine, N 1 -acetylspermine, and N 1 -acetylspermidine. These BAL fluids and exogenous polyamines were able to induce apoptosis in alveolar macrophages. Apoptosis of alveolar macrophages during infection, after incubation with BAL fluids from Pneumocystis-infected animals, or after incubation with polyamines was marked by an increase in intracellular reactive oxygen species, activation of caspases-3 and -9, DNA fragmentation, and leakage of mitochondrial cytochrome c into the cytoplasm. When polyamines were depleted from the BAL fluids of infected animals, the ability of these BAL fluids to induce apoptosis was lost. Interestingly, the apoptosis inducing activity of the polyamine-depleted BAL fluids was restored when polyamines were added back. The results of this study suggested that Pneumocystis infection results in accumulation of high levels of polyamines in the lung. These polyamines activate apoptosis of alveolar macrophages, perhaps because of the ROS that are produced during polyamine metabolism.Pneumocystis-infected lungs usually contain much alveolar exudate and numerous inflammatory cells in perivascular and peribronchiolar areas (1-3). The infection also causes changes in the lung. One such change is significantly increased levels of surfactant proteins A and D (4, 5). These collectins are implicated in the attachment of Pneumocystis to alveolar epithelial cells during infection (4 -6) and evasion of the host immune response (7). In contrast, surfactant proteins B (8) and C (4, 9) are down-regulated in their expression. Macrophage mannose receptor expression is also down-regulated (10), although the shed form of the mannose receptor is increased (11), which may help the organism evade host immune responses (7,10,11). The expression of the transcription factor GATA-2 is reduced in alveolar macrophages during Pcp 2 (12), and this GATA-2 down-regulation is correlated with the dysfunction of alveolar macrophages (13). There is a decrease in plasma S-adenosylmethionine levels during the infection (14). The infection also causes erosion of type I pneumocytes and proliferation of type II epithelial cells (15). These changes indicate that Pneumocystis mediates many alterations in pulmonary and systemic environments in an effort to survive in the host.In addition to these changes, the number of alveolar macrophages is decreased during Pcp in humans (16 -20) and in a rat model of infection (21). This change may be due to decreased precursor cell recruitment or maturation, increased efflux of cells from the lung, increased apoptosis rate, or a combination of these factors. Apoptosis is a normal event in development or tissue turnover (22) and can also be a response to disease stat...

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P. cariniiinduces selective alterations in component expression and biophysical activity of lung surfactant

Cited by 62 publications

References 62 publications

IL-4 and IL-13 Form a Negative Feedback Circuit with Surfactant Protein-D in the Allergic Airway Response

IL-4 and IL-13 Form a Negative Feedback Circuit with Surfactant Protein-D in the Allergic Airway Response

Surfactant for Pediatric Acute Lung Injury

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

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