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Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor

Title: Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 beta-glucan receptor
Authors: Chad Steele; Luis Marrero; Steve Swain; Allen G. Harmsen; Mingquan Zheng; Gordon D. Brown; Siamon Gordon; Judd E. Shellito; Jay K. Kolls
Contributors: The Pennsylvania State University CiteSeerX Archives
Source: ftp://ftp.ncbi.nlm.nih.gov/pub/pmc/d8/51/J_Exp_Med_2003_Dec_1_198(11)_1677-1688.tar.gz
Publication Year: 2003
Collection: CiteSeerX
Description: Innate immune mechanisms against Pneumocystis carinii, a frequent cause of pneumonia in immunocompromised individuals, are not well understood. Using both real time polymerase chain reaction as a measure of organism viability and fluorescent deconvolution microscopy, we show that nonopsonic phagocytosis of P. carinii by alveolar macrophages is mediated by the Dectin-1 �-glucan receptor and that the subsequent generation of hydrogen peroxide is involved in alveolar macrophage–mediated killing of P. carinii. The macrophage Dectin-1 �-glucan receptor colocalized with the P. carinii cyst wall. However, blockage of Dectin-1 with high concentrations of anti–Dectin-1 antibody inhibited binding and concomitant killing of P. carinii by alveolar macrophages. Furthermore, RAW 264.7 macrophages overexpressing Dectin-1 bound P. carinii at a higher level than control RAW cells. In the presence of Dectin-1 blockage, killing of opsonized P. carinii could be restored through Fc�RII/III receptors. Opsonized P. carinii could also be efficiently killed in the presence of Fc�RII/III receptor blockage through Dectin-1–mediated phagocytosis. We further show that Dectin-1 is required for P. carinii–induced macrophage inflammatory protein 2 production by alveolar macrophages. Taken together, these results show that nonopsonic phagocytosis and subsequent killing of P. carinii by alveolar macrophages is dependent upon recognition by the Dectin-1 �-glucan receptor. Key words: lung • leukocyte • innate • yeast • chemokine
Document Type: text
File Description: application/zip
Language: English
Relation: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.282.4084
Availability: http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.282.4084
Rights: Metadata may be used without restrictions as long as the oai identifier remains attached to it.
Accession Number: edsbas.D390D9B1
Database: BASE