Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages.

O’Riordan, Deirdre; Standing, Joseph E.; Kwon, Kun Young; Chang, Donald; Crouch, Edmond C.; Limper, Andrew H.

doi:10.1172/jci117972

Cited by 159 publications

(131 citation statements)

References 64 publications

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“…Analysis of the peptide sequence of the gp70 molecule from S. schenckii shows significant homology with a 89-kDa major surface glycoprotein 110 of P. carinii (msg 110). Some authors have reported that the msg 110 from P. carinii is involved in attachment to epithelial cells [29][30][31]. It has been previously shown that during the interaction of S. schenckii yeast cells with endothelial cell monolayers, a significant amount of yeast is found at the intercellular junctions.…”

Section: Discussionmentioning

confidence: 99%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that specific antibodies show different degrees of protection against mycosis. In a previous study, antigens secreted by Sporothrix schenckii induced a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of antibodies to this antigen in infection control. In the present study, an IgG1 mAb was produced against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell-deficient mice were used. Moreover, in a second schedule treatment, the mAb was injected after infection was established, and again we observed a significant reduction in CFU associated with an increase of IFN-cproduction. Also, the 70-kDa antigen is shown to be a putative adhesin present on the surface of this fungus. In conclusion, we report for the first time the protective effect of a specific antibody against S. schenckii.Key words: Adhesins . Mab . Passive immunization . Sporothrix schenckii . Sporotrichosis IntroductionSporotrichosis is a chronic subcutaneous mycosis that occurs worldwide. However, this disease is commonly seen in tropical and subtropical regions [1]. It is caused by traumatic inoculation of the dimorphic fungus Sporothrix schenckii, which is an ubiquitous environmental saprophyte that can be isolated from soil and plant debris [2]. In the past, infections were limited to the cutaneous forms of the disease.Recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromised individuals [3,4].The immunological mechanisms involved in prevention and control of sporotrichosis suggest that cell-mediated immunity plays an important role in protecting The host against S. schenckii [5]. In experimental infections, athymic nude mice are more susceptible to sporotrichosis, and acquired immunity against S. schenckii is mainly mediated by T-cell-activated macrophages [6,7].In contrast, the role of the humoral immune response in protection against this fungus has not been studied in detail. In a previous study, we showed that antigens secreted by S. 3080induce a specific humoral response in infected animals, mainly against the 70-kDa molecule, indicating a possible participation of specific antibodies to this molecule in infection control [8].Cell-mediated and innate immunity are considered the most important mechanisms of host defense against fungus infections. However, recent studies demonstrated that antibodies with defined specificity show different degrees of protection against mycosis [9]. Administration of mAb-mediated protection against Paracoccidioides brasiliensis and Candida albicans and modif...

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Section: Discussionmentioning

confidence: 99%

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

et al. 2008

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“…The development of Pneumocystis carinii enhances these abnormalities [78]. During P. carinii pneumonia, SP-D accumulates in the lung [191], interacts with gpA (the major surface antigen of P. carinii), and augments the binding of P. carinii to alveolar macrophages [227]. SP-D interacts with the mannose-rich antigen gp120, which modulates an interaction with the alveolar macrophages.…”

Section: Protection Against Nonbacterial Microorganisms and Virusesmentioning

confidence: 99%

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

Creuwels

Golde

Haagsman

1997

Lung

282

188

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Abstract. This article starts with a brief account of the history of research on pulmonary surfactant. We will then discuss the morphological aspects and composition of the pulmonary surfactant system. We describe the hydrophilic surfactant proteins A and D and the hydrophobic surfactant proteins B and C, with focus on the crucial roles of these proteins in the dynamics, metabolism, and functions of pulmonary surfactant. Next we discuss the major disorders of the surfactant system. The final part of the review will be focused on the potentials and complications of surfactant therapy in the treatment of some of these disorders. It is our belief that increased knowledge of the surfactant system and its functions will lead to a more optimal composition of the exogenous surfactants and, perhaps, widen their applicability to treatment of surfactant disorders other than neonatal respiratory distress syndrome.Key words: Surfactant protein-Pulmonary surfactant-Respiratory distress syndrome. HistoryResearch on surfactant goes back to 1929 when von Neergaard published the first paper about the difference in pressure needed to inflate lungs with air or with liquid [333]. He found that the pressure necessary for filling the lungs with air was higher than when the lungs were filled with liquid. To explain this result he stated that the alveoli were stabilized by lowering the naturally high surface tension of the air/water interface. In 1946 Thannhauser and co-workers reported that lung tissue has a remarkably high content of the lipid dipalmityl lecithin (current name, dipalmitoylphosphatidylcholine)Offprint requests to: Henk P. Haagsman.

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“…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).…”

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confidence: 99%

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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Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages.

Abstract: Invest. 1995Invest. . 95:2699Invest. -2710

Cited by 159 publications

References 64 publications

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

Passive immunization with monoclonal antibody against a 70‐kDa putative adhesin of Sporothrix schenckii induces protection in murine sporotrichosis

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

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