Expression and Characterization of a cDNA Clone Encoding an Immunodominant Surface Glycoprotein of Pneumocystis carinii

Haidaris, Patricia J.; Wright, Terry W.; Gigliotti, Francis; Haidaris, Constantine G.

doi:10.1093/infdis/166.5.1113

Cited by 88 publications

(68 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total RNA was isolated from uninfected and infected ECs at 3, 7, 14, and 21 hpi by using Tri-Reagent (Molecular Research Center, Inc., Cincinnati, Ohio) according to the manufacturer's instructions. Northern blot analysis was performed essentially as described previously (14). Briefly, 20 g of total RNA per condition was denatured in a glyoxal-dimethyl sulfoxide mix and then separated by electrophoresis in 1.4% agarose gels with 10 mM sodium phosphate buffer (pH 7.0) with recirculation.…”

Section: Methodsmentioning

confidence: 99%

NF-κB Activation duringRickettsia rickettsiiInfection of Endothelial Cells Involves the Activation of Catalytic IκB Kinases IKKα and IKKβ and Phosphorylation-Proteolysis of the Inhibitor Protein IκBα

Clifton¹,

Rydkina²,

Freeman

et al. 2005

Infect Immun

View full text Add to dashboard Cite

Rocky Mountain spotted fever, caused by the obligate intracellular bacterial pathogen Rickettsia rickettsii, is one of the most frequently reported and severe rickettsial diseases in the United States. R. rickettsii primarily invades vascular endothelial cells (ECs) in humans, replicates predominantly within the cytoplasm, and utilizes actin polymerization-based directional motility for intracellular movements and intercellular spread (19,42). The vascular endothelium is a multifunctional endocrine and paracrine organ involved in the modulation of blood flow and vessel tone, coagulation, and regulation of immune and inflammatory responses. In general, an intricate relationship between activation of immune responses and modulation of coagulation properties, usually followed by dysregulation of hemostatic mechanisms, is a hallmark feature of infectious diseases affecting the endothelium (2, 45). A majority of pathological sequelae associated with spotted fever group rickettsioses are attributed to damage of ECs affecting these functions in severe cases of infection (41, 42). ECs not only participate in the uptake of viable Rickettsia organisms attached to the cell surface through "induced phagocytosis," resulting in internalization, but actively respond to infection by adjusting the expression of mediators with important physiological functions such as adhesion molecules, cytokines, chemokines, and regulatory components of the coagulation cascade (8,40). Many of these genes are regulated by the nuclear factor-B (NF-B)/ Rel family of transcription factors, known to play an important role in immediate-early pathogenic responses (1, 2, 12).The prototypical NF-B complex is a heterodimer of RelA (p65) and p50 (NFKB1) subunits; other members of the Rel family include c-Rel, RelB, and p52 (NFKB2). In resting cells, NF-B is sequestered in the cytoplasm in its latent form through association with inhibitory proteins termed IB (IB␣, IB␤, IB␥, IBε, p105, and p100). Upon appropriate cell stimulation, IB␣ and IB␤ are rapidly phosphorylated on specific amino-terminal serines, signaling for ubiquitination and degradation by the 26S proteasome (12,46). This results in the exposure of a nuclear localization sequence (NLS) and DNA-binding domains, allowing NF-B to enter the nucleus and stimulate the transcription of target genes. One such target is IB␣ itself, the resynthesis of which completes an autoreg-* Corresponding author. Mailing address: Hemostasis and Throm-

show abstract

Section: Methodsmentioning

confidence: 99%

NF-κB Activation duringRickettsia rickettsiiInfection of Endothelial Cells Involves the Activation of Catalytic IκB Kinases IKKα and IKKβ and Phosphorylation-Proteolysis of the Inhibitor Protein IκBα

Clifton¹,

Rydkina²,

Freeman

et al. 2005

Infect Immun

View full text Add to dashboard Cite

show abstract

“…Ultrastructural and in vitro experiments demonstrate that macrophages bind and internalize P. carinii (12,13,17,20,24). Macrophage mannose receptors mediate uptake of the organisms through interaction with glycoprotein A (gpA), 1 a 120-kD antigenic complex present on the surface of P. carinii (17,20,(25)(26)(27)(28)(29)(30)(31)(32). Additional in vitro studies demonstrate that interaction of P. carinii with alveolar macrophages causes release of proinflammatory substances including reactive oxidants, arachidonic acid metabolites, and TNF-␣ (18,19,21,33,34).…”

Section: Introductionmentioning

confidence: 99%

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

Limper¹,

Hoyte²,

Standing³

1997

J. Clin. Invest.

173

149

View full text Add to dashboard Cite

Although studies indicate that alveolar macrophages participate in host defense against Pneumocystis carinii , their role in organism degradation and clearance from the lung has not yet been established. We, therefore, quantified the uptake and degradation of 35 S-labeled P. carinii by cultured macrophages, demonstrating significant degradation of P. carinii over 6 h. We further evaluated the role of macrophages in elimination of P. carinii from the living host. Rats received either intratracheal PBS, liposomal PBS (L-PBS), or liposomal dichloromethylene diphosphonate (L-Cl 2 MDP), a preparation which leads to selective depletion of macrophages. Over 72 h, L-Cl 2 MDP-treated animals had loss of Ͼ 85% of their alveolar macrophages. In contrast, L-PBS-treated rats had cellular differentials identical to rats receiving PBS. Macrophage-depleted rats and controls were next inoculated with P. carinii and organism clearance was determined after 24 h. P. carinii elimination was evaluated with both cyst counts and an ELISA directed against glycoprotein A (gpA), the major antigen of P. carinii . Both assays indicated that macrophage-depleted rats had substantial impairment of P. carinii clearance compared to L-PBS-or PBS-treated rats. These data provide the first direct evidence that macrophages mediate elimination of P. carinii from the living host. ( J. Clin. Invest. 1997. 99:2110-2117.)

show abstract

“…carindi possesses several carbohydrate-rich surface proteins capable of interacting with lectins and other glycoproteins (35)(36)(37)(38)(39). In particular, P. carinji contains a major surface glycoprotein complex which has been variously termed gpA, gp 95, gpl2O, or major surface glycoprotein (40)(41)(42)(43)(44)(45). Differences in the relative molecular mass of this complex have been related to the host species from which the P. carinii are derived (35).…”

Section: Introductionmentioning

confidence: 99%

“…Differences in the relative molecular mass of this complex have been related to the host species from which the P. carinii are derived (35). Therefore, a number of investigators have adopted the nomenclature of gpA for this glycoprotein complex (44)(45)(46)(47). Molecular studies indicate that gpA is encoded by a family of genes containing relatively conserved cysteine-rich regions (41,42,45,46).…”

Section: Introductionmentioning

confidence: 99%

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

O’Riordan¹,

et al. 1995

View full text Add to dashboard Cite

show abstract

Expression and Characterization of a cDNA Clone Encoding an Immunodominant Surface Glycoprotein of Pneumocystis carinii

Cited by 88 publications

References 38 publications

NF-κB Activation duringRickettsia rickettsiiInfection of Endothelial Cells Involves the Activation of Catalytic IκB Kinases IKKα and IKKβ and Phosphorylation-Proteolysis of the Inhibitor Protein IκBα

NF-κB Activation duringRickettsia rickettsiiInfection of Endothelial Cells Involves the Activation of Catalytic IκB Kinases IKKα and IKKβ and Phosphorylation-Proteolysis of the Inhibitor Protein IκBα

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

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

Contact Info

Product

Resources

About