scholarly journals Pneumocystis carinii induces an oxidative burst in alveolar macrophages.

1992 ◽  
Vol 60 (1) ◽  
pp. 1-7 ◽  
Author(s):  
H A Hidalgo ◽  
R J Helmke ◽  
V F German ◽  
J A Mangos
Keyword(s):  
Alveolar Macrophages ◽  
Oxidative Burst ◽  
Pneumocystis Carinii

scholarly journals Passive Immunization of Neonatal Mice against Pneumocystis carinii f. sp. muris Enhances Control of Infection without Stimulating Inflammation

2004 ◽  
Vol 72 (11) ◽  
pp. 6211-6220 ◽  
Author(s):  
Kerry M. Empey ◽  
Melissa Hollifield ◽  
Kevin Schuer ◽  
Francis Gigliotti ◽  
Beth A. Garvy
Keyword(s):  
Alveolar Macrophage ◽  
Specific Antibody ◽  
Alveolar Macrophages ◽  
Macrophage Activation ◽  
Pneumocystis Carinii ◽  
Passive Immunization ◽  
Activation Markers ◽  
Effector Cells ◽  
Macrophage Activity ◽  
Neonatal Mice

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to infection with Pneumocystis. We have previously shown that there is a significant delay in clearance of the organisms from the lungs of neonatal mice compared to adults. Since alveolar macrophages are the effector cells responsible for killing and clearance of Pneumocystis, we have examined alveolar macrophage activity in neonatal mice. We found that alveolar macrophage activation is delayed about 1 week in Pneumocystis-infected neonates compared to adults. Opsonization of the organism by Pneumocystis-specific antibody resulted in increased clearance of the organism in neonatal mice; however, there was decreased expression of activation markers on neonatal alveolar macrophages and reduced levels of cytokines associated with macrophage activation. Mice born to immunized dams had significant amounts of Pneumocystis-specific immunoglobulin G in their lungs and serum at day 7 postinfection, whereas mice born to naïve dams had merely detectable levels. This difference correlated with enhanced Pneumocystis clearance in mice born to immunized dams. The increase in specific antibody, however, did not result in significant inflammation in the lungs, as no differences in numbers of activated CD4+ cells were observed. Furthermore, there was no difference in cytokine or chemokine concentrations in the lungs of pups born to immune compared to naïve dams. These findings indicate that specific antibody plays an important role in Pneumocystis clearance from lungs of infected neonates; moreover, this process occurs without inducing inflammation in the lungs.

scholarly journals Effect of Transcription Factor GATA-2 on Phagocytic Activity of Alveolar Macrophages from Pneumocystis carinii-Infected Hosts

2003 ◽  
Vol 71 (9) ◽  
pp. 4943-4952 ◽  
Author(s):  
Mark E. Lasbury ◽  
Xing Tang ◽  
Pamela J. Durant ◽  
Chao-Hung Lee
Keyword(s):  
Transcription Factor ◽  
Alveolar Macrophages ◽  
Phagocytic Activity ◽  
Pneumocystis Carinii ◽  
Fluorescein Isothiocyanate ◽  
Cmv Promoter ◽  
Latex Beads ◽  
Expression Construct ◽  
Sense Orientation ◽  
General Defect

ABSTRACT Alveolar macrophages from Pneumocystis carinii-infected hosts are defective in phagocytosis (W. Chen, J. W. Mills, and A. G. Harmsen, Int. J. Exp. Pathol. 73:709-720, 1992; H. Koziel et al., J. Clin. Investig. 102:1332-1344, 1998). Experiments were performed to determine whether this defect is specific for P. carinii organisms. The results showed that these macrophages were unable to phagocytose both P. carinii organisms and fluorescein isothiocyanate (FITC)-conjugated latex beads, indicating that alveolar macrophages from P. carinii-infected hosts have a general defect in phagocytosis. To determine whether this defect correlates with the recently discovered down-regulation of the GATA-2 transcription factor gene during P. carinii infection, alveolar macrophages from dexamethasone-suppressed or healthy rats were treated with anti-GATA-2 oligonucleotides and then assayed for phagocytosis. Aliquots of the alveolar macrophages were also treated with the sense oligonucleotides as the control. Cells treated with the antisense oligonucleotides were found to have a 46% reduction in phagocytosis of P. carinii organisms and a 65% reduction in phagocytosis of FITC-latex beads compared to those treated with the sense oligonucleotides. To determine whether the defect in phagocytosis in alveolar macrophages from P. carinii-infected hosts can be corrected by overexpression of GATA-2, a plasmid containing the rat GATA-2 gene in the sense orientation driven by the cytomegalovirus (CMV) promoter was introduced into alveolar macrophages from P. carinii-infected rats. Aliquots of the same cells transfected with a plasmid containing GATA-2 in the antisense orientation relative to the CMV promoter served as the control. Alveolar macrophages treated with the sense GATA-2 expression construct were found to increase their phagocytic activity by 66% in phagocytosis of P. carinii organisms and by 280% in phagocytosis of FITC-latex beads compared to those that received the antisense GATA-2 construct. The results of this study indicate that GATA-2 plays an important role in the regulation of phagocytosis in alveolar macrophages during P. carinii infection.

Particulate Load From Biomass Smoke Is Associated With Increased Oxidative Burst And Reduced Proteolysis in Alveolar Macrophages

2010 ◽  
Author(s):  
Duncan G. Fullerton ◽  
David Mzinza ◽  
Sarah Glennie ◽  
Kondwani Jambo ◽  
Steve Barrett ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Oxidative Burst ◽  
Biomass Smoke

scholarly journals Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice

2007 ◽  
Vol 75 (7) ◽  
pp. 3382-3393 ◽  
Author(s):  
Kerry M. Empey ◽  
Melissa Hollifield ◽  
Beth A. Garvy
Keyword(s):  
Escherichia Coli ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Pneumocystis Carinii ◽  
Effector Cells ◽  
Macrophage Activity ◽  
Adult Mice

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to Pneumocystis pulmonary infections. We have previously demonstrated that there is approximately a 3-week delay in the clearance of Pneumocystis organisms from pup mouse lungs compared to that in adults. We have further shown that there is approximately a 1-week delay in alveolar macrophage activation in pups versus adult mice. Alveolar macrophages are the primary effector cells responsible for the killing and clearance of Pneumocystis, suggesting that pup alveolar macrophages may be involved in the delayed clearance of this organism. Alveolar macrophages cultured in vitro with Pneumocystis alone demonstrate little to no activation, as indicated by a lack of cytokine production. However, when cultured with lipopolysaccharide (LPS) or zymosan, cytokine production was markedly increased, suggesting that pup alveolar macrophages are specifically unresponsive to Pneumocystis organisms rather than being intrinsically unable to become activated. Furthermore, pup mice treated with aerosolized, heat-killed Escherichia coli in vivo were able to clear Pneumocystis more efficiently than were control mice. Together, these data suggest that while pup alveolar macrophages are unresponsive to P. carinii f. sp. muris organisms, they are capable of activation by heat-killed E. coli in vivo, as well as LPS and zymosan in vitro. The lack of response of pup mice to P. carinii f. sp. muris may reflect protective mechanisms specific to the developing pup lung, but ultimately it results in insufficient clearance of Pneumocystis organisms.

scholarly journals Effect of Bronchoalveolar Lavage Fluid from Pneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

2004 ◽  
Vol 72 (4) ◽  
pp. 2140-2147 ◽  
Author(s):  
Mark E. Lasbury ◽  
Peimao Lin ◽  
Dennis Tschang ◽  
Pamela J. Durant ◽  
Chao-Hung Lee
Keyword(s):  
Bronchoalveolar Lavage ◽  
Concanavalin A ◽  
Alveolar Macrophages ◽  
Phagocytic Activity ◽  
Pneumocystis Carinii ◽  
Surface Glycoprotein ◽  
Suppressive Activity ◽  
Agarose Beads ◽  
Major Surface Glycoprotein ◽  
Major Surface

ABSTRACT Alveolar macrophages from Pneumocystis carinii-infected rats are defective in phagocytosis. To investigate whether this defect is due to a certain factor present in P. carinii-infected lungs, alveolar macrophages from uninfected rats were incubated with bronchoalveolar lavage (BAL) fluid samples from P. carinii-infected rats. Alveolar macrophages treated with these BAL fluid samples became defective in phagocytosis but remained normal when treated with BAL fluid samples from noninfected or Toxoplasma gondii-infected rats. The suppressive activity of the BAL fluid samples from P. carinii-infected rats on phagocytosis was retained when the BAL fluid samples were passed through a filter with a pore size of 0.45 μm but was lost when the BAL fluid samples were digested with proteases such as trypsin, pepsin, papain, or endopeptidase Gly-C. Lipid fractions of these BAL fluid samples had no suppressive activity on phagocytosis. The suppressive activity of these BAL fluid samples was also lost when they were incubated with concanavalin A-agarose beads, suggesting that the inhibitor is a glycoprotein. The inhibitor was estimated to be larger than 100,000 Da by exclusion filtration. After binding to the concanavalin A-agarose beads, the inhibitor in BAL fluid samples and P. carinii lysate could be eluted with 200 mM methylmannose. Treatment of both the crude BAL fluid samples and P. carinii lysate and the 200 mM methylmannose eluate with antibody against the major surface glycoprotein of P. carinii eliminated their suppressive activity. These results suggest that the factor capable of suppressing the phagocytic activity of alveolar macrophages is P. carinii major surface glycoprotein or one or more of its derivatives.

scholarly journals Mechanism of Pneumocystis carinii attachment to cultured rat alveolar macrophages.

1990 ◽  
Vol 86 (5) ◽  
pp. 1678-1683 ◽  
Author(s):  
S T Pottratz ◽  
W J Martin
Keyword(s):  
Alveolar Macrophages ◽  
Pneumocystis Carinii

scholarly journals The role of alveolar macrophages in Pneumocystis carinii degradation and clearance from the lung.

1997 ◽  
Vol 99 (9) ◽  
pp. 2110-2117 ◽  
Author(s):  
A H Limper ◽  
J S Hoyte ◽  
J E Standing
Keyword(s):  
Alveolar Macrophages ◽  
Pneumocystis Carinii
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