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KMID : 0043320070300111440
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Archives of Pharmacal Research
2007 Volume.30 No. 11 p.1440 ~ p.1446
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Dendritic Cells Process Antigens Encapsulated in a Biodegradable Polymer, Poly(D,L-lactide-co-glycolide), via an Alternate Class I MHC Processing Pathway
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Gerelchuluun Turmunkh
Lee Young-Hee
Lee Young-Ran
Lim Seon-A
Song Suk-Gil
Park Jeong-Sook
Han Kun
Kim Kyung-Jae
Lee Chong-Kil
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Abstract
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Biodegradable nanospheres generated from a biocompatible polymer, poly(D,L-lactide-co-glycolide) (PLGA), have been studied extensively as implantable reservoirs for sustained-release drug delivery. PLGA-nanospheres have also been studied as vehicles to deliver antigens to phagocytes. The intracellular processing pathway of antigens delivered to phagocytes by PLGA particles was studied in the present study. Ovalbumin (OVA) encapsulated with PLGA (OVA-nanosphere) was efficiently captured, processed and presented on class I major histocompatibility complex (MHC-I) by dendritic cells (DCs). The MHC-I processing of OVA-nanospheres was resistant to lactacystin, a proteosome inhibitor, and brefeldin A, which blocks anterograde transport from the endoplasmic reticulum (ER) through the Golgi apparatus. Chloroquine, which inhibits phagolysosomal enzymes by increasing phagolysosomal pH, inhibited MHC-I processing of OVA-nanospheres. In addition, DCs generated from TAP-/- mice were markedly suppressed in MHC-I processing of OVA-nanospheres. These results demonstrate that DCs process phagocytosed OVA뻨anospheres via a vacuolar alternate MHC-I pathway for presentation of OVA peptides to T lymphocytes
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KEYWORD
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Dendritic cell, Cross-presentation, PLGA nanosphere, Lactacystin, Brefeldin A, Chloroquine
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