Incorporation of Fatty Acids and Amino Acids by Cultured <i>Pneumocystis carinii</i>

Paulsrud, John R.; Queener, Sherry F.

doi:10.1111/j.1550-7408.1994.tb01525.x

Cited by 19 publications

(23 citation statements)

References 24 publications

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“…An inflammatory response (51,54), changes in macrophage and polymorphonuclear cell populations (11,53,55), and proliferation of organisms also occur during Pneumocystis infection. Pneumocystis organisms also interact with host cells and alveolar constituents to scavenge important factors such as fatty acids and lipids (21,42). Whether any of these factors or actions has any impact on the suppressive effect of the inhibitor remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

et al. 2004

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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 m 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.An important function of alveolar macrophages is to clear foreign particles and infectious agents from the lung. Their role in the defense against Pneumocystis carinii infection is demonstrated by the observation that transtracheally inoculated P. carinii organisms are not cleared in alveolar macrophage-depleted rats (31). Administration of granulocyte-macrophage colony-stimulating factor, which activates alveolar macrophages (40), decreases the severity of P. carinii pneumonia (34). This finding also indicates the importance of alveolar macrophages in the clearance of Pneumocystis organisms.The alveoli are constantly exposed to foreign material and microorganisms. The alveolar macrophage maintains a low level of activation to engulf and destroy these materials while inhibiting an overly reactive inflammatory reaction to foreign objects encountered. To accomplish this, alveolar macrophages inhibit antigen presentation by dendritic cells (20), limit the expansion of lymphocyte populations (38), and restrict pulmonary lymphocyte functions (19). When activated, alveolar macrophages become proinflammatory and produce interleukin-8, which attracts neutrophils and lymphocytes by chemotaxis, as well as interleukin-1␤, tumor necrosis factor alpha, interleukin-6, and granulocyte-macrophage colony-stimulating factor, wh...

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Section: Discussionmentioning

confidence: 99%

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

et al. 2004

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“…In considering the difficulties faced in studying P. carinii by direct analytical biochemistry, significant advances have been made with respect to its lipids within the last decade (47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Over 20 sterol components have been detected in rat-derived P. carinii carinii (5-7,53,58) and human-derived P. carinii hominis (6-8,60) ( Table 1).…”

Section: Sterols In Pneumocystis Isolated From Rat and Human Pcp Lungsmentioning

confidence: 99%

C₂₇ to C₃₂ sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals

Kaneshiro

Wyder

2000

Lipids

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Pneumocystis carinii is the paradigm of opportunistic infections in immunocompromised mammals. Prior to the acquired immunodeficiency syndrome (AIDS) pandemic and the use of immunosuppressive therapy in organ transplant and cancer patients, P. carinii was regarded as a curiosity, rarely observed clinically. Interest in this organism exploded when it was identified as the agent of P. carinii pneumonia (PcP), the direct cause of death among many AIDS patients. Aggressive prophylaxis has decreased the number of acute PcP cases, but it remains among the most prevalent opportunistic infections found within this patient population. The taxonomic assignment of P. carinii has long been argued; molecular genetics data now demonstrate that it is a fungus. Several antimycotic drugs are targeted against ergosterol or its biosynthesis, but these are not as effective against PcP as they are against other fungal infections. This can now be explained in part by the identification of the sterols of P. carinii. The organism lacks ergosterol but contains distinct C28 and C29 delta7 24-alkylsterols. Also, 24-methylenelanost-8-en-3beta-ol (C31) and pneumocysterol, (24Z)-ethylidenelanost-8-en-3beta-ol (C32) were recently identified in organisms infecting humans. Together, the delta7 24-alkylsterols and pneumocysterol are regarded as signature lipids of the pathogen that can be useful for the diagnosis of PcP, since no other lung pathogen is known to contain them. Cholesterol (C27), the dominant sterol component in P. carinii, is probably totally scavenged from the host. De novo synthesis of sterols has been demonstrated by the presence of lovastatin-sensitive 3-hydroxy-3-methylglutaryl-CoA reductase activity, the incorporation of radiolabeled mevalonate and squalene into P. carinii sterols, and the reduction in cellular ATP in cells treated with inhibitors of enzymes in sterol biosynthesis.

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“…Similarly, Amoeba does not take up radiolabeled glucose unless pinocytotic activity is induced. It appears that Pneumocystis is similar to Paramecium in that they both take up and metabolize exogenous lipids much faster than amino acids [8,12,17,18,211. The rates of uptake and metabolism of exogenous material P21.…”

Section: Incorporation Of Radiolabeled Serine Into P Curinii Lipidsmentioning

confidence: 99%

Uptake and Metabolism of L‐Serine by Pneumocystis carinii carinii

Florín-Christensen

Florin‐Christensen

Kaneshiro

1995

J Eukaryotic Microbiology

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Serine is an important amino acid that is utilized in the biosyntheses of proteins and lipids. It is directly incorporated into the head group of phosphatidylserine, which in turn can be converted to other phospholipids. Also, it is required for the formation of long chain bases, precursors of sphingolipids. Uptake and incorporation of radiolabeled serine into both lipids and acid-precipitable material were demonstrated in Pneumocystis carinii carinii organism preparations freshly isolated from infected rat lungs. Radioactivity in proteins was about double that observed in lipids. Liquid scintillation spectrometry of metabolically radiolabeled lipids separated by thin-layer chromatography showed 53% of the total radioactivity were in phosphatidylserine, 12% in phosphatidylethanolamine, 24% in ceramides, and 11% in long chain bases and other compounds. Four long chain bases were detected by thin-layer chromatography in hydrolyzed P. carinii ceramides metabolically labeled with radioactive serine. Phytosphingosine and dihydrosphingosine were tentatively identified by their migrations on thin-layer plates. Radiolabeled ethanolamine was incorporated into P. carinii phosphatidylethanolamine, but relatively low incorporation of radiolabeled choline into phosphatidylcholine occurred. The observations made in this study indicated that P. carinii has the biosynthetic capacity to metabolize phospholipid head groups and to de novo synthesize sphingolipids. L-Cycloserine and beta-Cl-D-alanine, inhibitors of long chain base synthesis, reduced the incorporation of serine into P. carinii long chain bases and ceramides, which supported the conclusion that the pathogen synthesizes sphingolipids.

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Incorporation of Fatty Acids and Amino Acids by Cultured Pneumocystis carinii

Cited by 19 publications

References 24 publications

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

C₂₇ to C₃₂ sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals

Uptake and Metabolism of L‐Serine by Pneumocystis carinii carinii

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Incorporation of Fatty Acids and Amino Acids by Cultured Pneumocystis carinii

Cited by 19 publications

References 24 publications

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

Effect of Bronchoalveolar Lavage Fluid fromPneumocystis carinii- Infected Hosts on Phagocytic Activity of Alveolar Macrophages

C27 to C32 sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals

Uptake and Metabolism of L‐Serine by Pneumocystis carinii carinii

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C₂₇ to C₃₂ sterols found in Pneumocystis, and opportunistic pathogen of immunocompromised mammals