| 1. |
- Foti, M., et al.
(författare)
-
P56Lck anchors CD4 to distinct microdomains on microvilli
- 2002
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:4, s. 2008-2013
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-surface microvilli play a central role in adhesion, fusion, and signaling processes. Some adhesion and signaling receptors segregate on microvilli but the determinants of this localization remain mostly unknown. In this study, we considered CD4, a receptor involved in immune response and HIV infection, and p56Lck, a CD4-associated tyrosine kinase. Analysis of CD4 trafficking reveals that p56Lck binds tightly to CD4 independently of its activation state and inhibits CD4 internalization. Electron microscopy analysis established that p56Lck mediates CD4 association with microvilli whereas biochemical data indicate that p56Lck expression renders CD4 insoluble by the nonionic detergent Triton X-100. In addition, cytoskeleton-disrupting agent increased CD4 solubility, suggesting the involvement of cytoskeletal elements in CD4 anchoring to microvilli. This concept was supported further by the observation that the lateral mobility of CD4 within the plasma membrane was decreased in cells expressing p56Lck. Finally, isolation of detergent-resistant membranes revealed that the complex CD4-p56Lck is enriched within these domains as opposed to conditions in which CD4 does not interact with p56Lck. In conclusion, our results show that p56Lck targets CD4 to specialized lipid microdomains preferentially localized on microvilli. This localization, which prevents CD4 internalization, might facilitate CD4-mediated adhesion processes and could correspond to the signaling site of the receptor.
|
|
| 2. |
- Holm, Åsa, et al.
(författare)
-
Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation : correlation with impaired translocation of PKCα and defective phagosome maturation
- 2001
-
Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 3:7, s. 439-447
-
Tidskriftsartikel (refereegranskat)abstract
- Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.
|
|
| 3. |
- Holm, Åsa, et al.
(författare)
-
Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages
- 2003
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 302:4, s. 653-658
-
Tidskriftsartikel (refereegranskat)abstract
- Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCα. To investigate a possible connection between PKCα and LPG’s effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCα (DN PKCα). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCα-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCα is involved in F-actin turnover in macrophages and that PKCα-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCα by LPG.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Salata, Luiz A, et al.
(författare)
-
Recent outcomes and perspectives of the application of bone morphogenetic proteins in implant dentistry.
- 2002
-
Ingår i: Clinical implant dentistry and related research. - 1523-0899. ; 4:1, s. 27-32
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the discovery of bone morphogenetic proteins (BMPs), the number of related studies has increased substantially, and more recent outcomes have cast encouraging perspectives on their use in reconstructive surgery. PURPOSE: The aim of the present review was to summarize the present knowledge about the use of BMPs in conjunction with dental implants based on the literature. MATERIALS AND METHODS: Scientific articles dealing with the use of growth factors and bone healing with or without dental implants were searched for on MEDLINE and critically scrutinized. RESULTS: Thirty-nine scientific reports formed the base for the present review. Whereas the osteoinductive capability of BMPs is well documented, studies on their effects in implant dentistry are still incipient. Preclinical and clinical studies did not show outstandingly good outcomes of the application of BMPs compared with conventional treatments or controls. CONCLUSIONS: The number of studies in the field of dental implantology in which BMPs have been used is still too small for establishing clinical protocols of their use in order to improve a recipient bone bed prior to implant placement or to enhance the integration process of an implant.
|
|
| 7. |
|
|
