Alveolar Damage in AIDS-Related Pneumocystis carinii Pneumonia

Benfield, Thomas; Prentø, Poul; Junge, Jette; Vestbo, Jørgen; Lundgren, Jens D

doi:10.1378/chest.111.5.1193

Cited by 43 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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.…”

mentioning

confidence: 99%

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

Lasbury

Merali

Durant

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

Lasbury

Merali

Durant

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases. In a previous paper (3) we suggested that the reduction of uPA activity observed in our AIDS patients favored the intraalveolar deposition of fibrin which, in tum, could be responsible for the altered clearance of pathogenic organisms from the alveoli and for the fibrogenic reaction often observed in patients with PCP (9). As in human lungs, in the lungs of immunosuppressed rats developing PCP, signs of fibrosis have been observed (41) as well as a decrease of uPA production by AMs (this study).…”

Section: Discussionmentioning

confidence: 66%

Plasminogen Activator Production in a Rat Model of Pneumocystis carinii Pneumonia

Angelici

Contini

Spezzano

et al. 2001

Microbiology and Immunology

View full text Add to dashboard Cite

Several studies have indicated that the serine protease urokinase-plasminogen-activator (uPA) is an important factor in host defense against pulmonary pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (HAL) samples of immunosuppressed rats both with and without PCP, we observed a decrease in uPA activity as well as a decrease in cell number. Urokinase-PA production by AMs was reduced in rats treated with cortisone alone. However, an increase in cell-associated uPA was observed in rats with PCP. This increase appears to be produced in response to P. carinii infection. In fact, when AMs obtained from untreated healthy or immunosuppressed uninfected rats were challenged with P. carinii, a significant increase in PA activity in cell Iysates was observed, though a lower response was obtained in cortisone-treated animals. Our results suggest that healthy AMs respond to the presence of P. carinii with an increase in uPA production and that this response in immunodepressed rat-AMs is partially impaired.

show abstract

“…The human response to Pneumocystis organisms causes type II alveolar cells reactive proliferation, which would result in lung interstitial fibrosis. [1,17,18] In recent years, many authors thought that alveolar injury in PCP is mainly caused by human inflammatory response and not the organism burden in lungs. [19] The exact route of transmission of Pneumocystis pneumonia is also not clear.…”

Section: Discussionmentioning

confidence: 99%

Imaging Characteristics ofPneumocystis pneumoniaafter Renal Transplantation

et al. 2010

View full text Add to dashboard Cite

Identification of Pneumocysis pneumonia (PCP) after renal transplantation has a great impact on early diagnosis and therapy, which could decrease its mortality. Due to a lack of characteristic clinical symptoms, imaging modalities became very important in the diagnosing PCP. Thirteen PCP patients after renal transplantation were reviewed. They underwent a series of chest radiographs and chest high-resolution CT scans. The common radiological presentations were bilateral diffuse symmetrical ground-glass and consolidation opacities, followed by pneumoceles or air-filled cysts or linear or reticular shadows. Groundglass attenuations were showed clearly on HRCT in 13 patients, while only 6 on CXR. Pneumoceles or cysts (n = 8) were seen only on HRCT. Air-filled cysts or pneumoceles within bilateral diffuse symmetrical ground-glass and consolidation opacities may be the characteristic of this disease. If combined with clinical data, the diagnosis of PCP could be established.

show abstract

Alveolar Damage in AIDS-Related Pneumocystis carinii Pneumonia

Cited by 43 publications

References 24 publications

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

Plasminogen Activator Production in a Rat Model of Pneumocystis carinii Pneumonia

Imaging Characteristics ofPneumocystis pneumoniaafter Renal Transplantation

Contact Info

Product

Resources

About