Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor.
Selective delivery of antiparasitic or antibacterial drugs into infected macrophages could be a promising approach for improved therapies. Methotrexate conjugate with branched chain polypeptides exhibited pronounced anti-Leishmania activity in vitro and in vivo as reported here earlier. To identify...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797066415430172672 |
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| author | Szabó, R Peiser, L Plüddemann, A Bösze, S Heinsbroek, S Gordon, S Hudecz, F |
| author_facet | Szabó, R Peiser, L Plüddemann, A Bösze, S Heinsbroek, S Gordon, S Hudecz, F |
| author_sort | Szabó, R |
| collection | OXFORD |
| description | Selective delivery of antiparasitic or antibacterial drugs into infected macrophages could be a promising approach for improved therapies. Methotrexate conjugate with branched chain polypeptides exhibited pronounced anti-Leishmania activity in vitro and in vivo as reported here earlier. To identify structural requirements for efficient uptake of branched polypeptides, we have studied murine bone marrow culture-derived macrophages (BMMphi) from 129/ICR mice. We report on the translocation characteristics of structurally closely related compounds labeled with 5(6)-carboxyfluorescein. We found that this process is dependent on experimental conditions (e.g. polypeptide concentration, incubation time, and temperature). Using specific inhibitors as well as macrophages from wild-type and class-A scavenger receptor knockout (SR-A -/-) mice, we demonstrated that SR-A was involved in the endocytosis of some polypeptides depending on their charge. Uptake could be blocked by unlabeled polypeptide, by SR-A inhibitors, and by specific anti-SR-A monoclonal antibody. The polyanionic polypeptide poly[Lys(Succ-Glu(1.0)-dl-Ala(3.8))] (SuccEAK) with high charge density translocated more efficiently than poly[Lys(Ac-Glu(1.0)-dl-Ala(3.8))] (AcEAK), which had a lower anionic charge density. On the basis of experimental data presented, SuccEAK can be considered as a potential candidate for the design of a macromolecular carrier for specific drug delivery of bioactive entities into macrophages via SR-A. |
| first_indexed | 2024-03-06T21:41:44Z |
| format | Journal article |
| id | oxford-uuid:482a1a45-2904-4217-905a-cdde6a365a72 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:41:44Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:482a1a45-2904-4217-905a-cdde6a365a722022-03-26T15:24:07ZUptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:482a1a45-2904-4217-905a-cdde6a365a72EnglishSymplectic Elements at Oxford2005Szabó, RPeiser, LPlüddemann, ABösze, SHeinsbroek, SGordon, SHudecz, FSelective delivery of antiparasitic or antibacterial drugs into infected macrophages could be a promising approach for improved therapies. Methotrexate conjugate with branched chain polypeptides exhibited pronounced anti-Leishmania activity in vitro and in vivo as reported here earlier. To identify structural requirements for efficient uptake of branched polypeptides, we have studied murine bone marrow culture-derived macrophages (BMMphi) from 129/ICR mice. We report on the translocation characteristics of structurally closely related compounds labeled with 5(6)-carboxyfluorescein. We found that this process is dependent on experimental conditions (e.g. polypeptide concentration, incubation time, and temperature). Using specific inhibitors as well as macrophages from wild-type and class-A scavenger receptor knockout (SR-A -/-) mice, we demonstrated that SR-A was involved in the endocytosis of some polypeptides depending on their charge. Uptake could be blocked by unlabeled polypeptide, by SR-A inhibitors, and by specific anti-SR-A monoclonal antibody. The polyanionic polypeptide poly[Lys(Succ-Glu(1.0)-dl-Ala(3.8))] (SuccEAK) with high charge density translocated more efficiently than poly[Lys(Ac-Glu(1.0)-dl-Ala(3.8))] (AcEAK), which had a lower anionic charge density. On the basis of experimental data presented, SuccEAK can be considered as a potential candidate for the design of a macromolecular carrier for specific drug delivery of bioactive entities into macrophages via SR-A. |
| spellingShingle | Szabó, R Peiser, L Plüddemann, A Bösze, S Heinsbroek, S Gordon, S Hudecz, F Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title | Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title_full | Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title_fullStr | Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title_full_unstemmed | Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title_short | Uptake of branched polypeptides with poly[L-lys] backbone by bone-marrow culture-derived murine macrophages: the role of the class a scavenger receptor. |
| title_sort | uptake of branched polypeptides with poly l lys backbone by bone marrow culture derived murine macrophages the role of the class a scavenger receptor |
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