Linked Life Data

17339468

Source:http://linkedlifedata.com/resource/pubmed/id/17339468

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-3-6
pubmed:abstractText
Pneumocystis carinii (PC) pneumonia is a leading opportunistic infection found among HIV-infected individuals worldwide. Although CD4(+) T cell deficiency clearly correlates with susceptibility to PC pneumonia, murine models of disease indicate that PC-directed Abs may prevent infection and/or inhibit growth of existing PC within the lungs. Recognition of PC by alveolar macrophages involves the beta-glucan receptor Dectin-1 and macrophage effector function against PC is enhanced by Abs derived from PC-vaccinated hosts. We developed a fusion protein consisting of the extracellular domain of Dectin-1 linked to the Fc portion of murine IgG1, which we hypothesized would enhance host recognition and opsonic phagocytosis of PC. The recombinant protein, Dectin-Fc, is dimeric and the Ag recognition site identifies beta-1,3 glucan linkages specifically and with high affinity (K(D) = 2.03 x 10(-7) M). Dectin-Fc enhances RAW264.7 macrophage recognition of the beta-glucan containing particulate zymosan in an FcgammaRII- and FcgammaRIII-dependent manner and preopsonization of PC organisms with Dectin-Fc increased alveolar and peritoneal macrophage-dependent killing of PC. SCID mice treated with a replication incompetent adenoviral vector expressing Dectin-Fc had attenuated growth of PC within the lungs, overall decreased PC lung burden, and diminished correlates of PC-related lung damage relative to SCID mice receiving a control vector. These findings demonstrate that targeting PC beta-glucan with Dectin-Fc enhances host recognition and clearance of PC in the absence of B and T cells, and suggest that FcgammaR-based targeting of PC, via cell wall carbohydrate recognition, may promote resistance against PC pneumonia in the immunodeficient host.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3702-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:17339468-AIDS-Related Opportunistic Infections, pubmed-meshheading:17339468-Adenoviridae, pubmed-meshheading:17339468-Animals, pubmed-meshheading:17339468-Antibody-Dependent Cell Cytotoxicity, pubmed-meshheading:17339468-Disease Models, Animal, pubmed-meshheading:17339468-Humans, pubmed-meshheading:17339468-Immunocompromised Host, pubmed-meshheading:17339468-Immunoglobulin Constant Regions, pubmed-meshheading:17339468-Lung, pubmed-meshheading:17339468-Macrophages, Alveolar, pubmed-meshheading:17339468-Male, pubmed-meshheading:17339468-Membrane Proteins, pubmed-meshheading:17339468-Mice, pubmed-meshheading:17339468-Mice, SCID, pubmed-meshheading:17339468-Nerve Tissue Proteins, pubmed-meshheading:17339468-Pneumocystis carinii, pubmed-meshheading:17339468-Pneumonia, Pneumocystis, pubmed-meshheading:17339468-Receptors, IgG, pubmed-meshheading:17339468-Recombinant Fusion Proteins, pubmed-meshheading:17339468-beta-Glucans
pubmed:year
2007
pubmed:articleTitle
Enhanced defense against Pneumocystis carinii mediated by a novel dectin-1 receptor Fc fusion protein.
pubmed:affiliation
Department of Pediatrics, Division of Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural