RESUMO
The role of metallic nano- and microparticles in the development of inflammation has not yet been investigated. Soft tissue biopsy specimens of the bone bed taken during surgical revisions, as well as supernatants obtained from the surface of the orthopedic structures and dental implants (control), were examined. Investigations were performed using X-ray microtomography, X-ray fluorescence analysis, and scanning electron microscopy. Histological studies of the bone bed tissues were performed. Nanoscale and microscale metallic particles were identified as participants in the inflammatory process in tissues. Supernatants containing nanoscale particles were obtained from the surfaces of 20 units of new dental implants. Early and late apoptosis and necrosis of immunocompetent cells after co-culture and induction by lipopolysaccharide and human venous blood serum were studied in an experiment with staging on the THP-1 (human monocytic) cell line using visualizing cytometry. As a result, it was found that nano- and microparticles emitted from the surface of the oxide layer of medical devices impregnated soft tissue biopsy specimens. By using different methods to analyze the cell-molecule interactions of nano- and microparticles both from a clinical perspective and an experimental research perspective, the possibility of forming a chronic immunopathological endogenous inflammatory process with an autoimmune component in the tissues was revealed.
Assuntos
Implantes Dentários , Humanos , Microscopia Eletrônica de Varredura , Monócitos , Linhagem Celular , Titânio/análise , Propriedades de SuperfícieRESUMO
OBJECTIVE: Dendritic cells (DC) play a key role in initiation of immune responses. In vitro modified acute myeloid leukemia (AML) blasts acquire certain specific features of DC and are suggested as a potential source of anti-leukemia vaccines. AML-DC have been characterized in terms of costimulatory molecule expression and cytokine production. In contrast, migratory capacity of AML-DC, which is a major attribute of DC required for their in vivo function, remains unknown. Here we present data on adhesion properties and profile of integrin expression of AML-DC. MATERIALS AND METHODS: Blasts from nine patients were used to generate AML-DC by calcium ionophore treatment. Adhesion of AML-DC to the major components of the extracellular matrix and the profile of integrin expression was studied using flow cytometry. RESULTS: Similar to their normal counterparts, calcium ionophore-induced AML-DC acquired the ability to bind to fibronectin and in 4 of 7 studied cases to bind to denatured collagen. Adhesion to native collagen remained unchanged during DC-type differentiation of AML blasts. AML-DC and DC obtained from monocytes of healthy donors expressed CD49d, CD49e, alphavbeta3, and alphavbeta5. However, AML-DC from 3 of 8 patients down-regulated CD49d, which plays an important role in cell-to-cell and cell-to-matrix interactions and normally is coexpressed with CD83. CONCLUSION: The results provide further evidence that AML blasts can be induced to display functional properties characteristic for DC and may prove useful for in vivo delivery and presentation of tumor antigens to the immune system. Abnormal CD49d expression and variability in AML-DC adhesion to denatured collagen indicate that motility of AML-DC from individual patients may vary, and a customized approach is essential for evaluating leukemic cell feasibility for vaccine design.
Assuntos
Crise Blástica/sangue , Adesão Celular/fisiologia , Células Dendríticas/imunologia , Integrinas/sangue , Ionóforos/farmacologia , Leucemia Mieloide/patologia , Linfoma/patologia , Adulto , Antígenos CD/sangue , Crise Blástica/imunologia , Feminino , Antígenos HLA-D/sangue , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Leucemia Mieloide/sangue , Leucemia Mieloide/imunologia , Linfoma/sangue , Linfoma/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/patologia , Valores de ReferênciaRESUMO
OBJECTIVES: The pattern of angiotensin-converting enzyme (ACE) expression in dendritic cells (DC) and macrophages derived from normal monocytes vs that in DC derived from acute myeloid leukemia blasts was investigated. MATERIALS AND METHODS: ACE expression was quantified by flow cytometry using a set of monoclonal antibodies (mAbs) directed against five different epitopes on the ACE molecule and by enzyme activity measurement. RESULTS: The binding pattern of a set of anti-ACE mAbs to the surface of blood cells and their progeny, as revealed by FACS, showed lineage and epitope specificity. Differentiation of monocytes to macrophages and DC was accompanied by a dramatic increase in ACE expression. ACE activity was 50-fold higher in macrophages and 150-fold higher in DC than in monocytes. ACE level normalized per cell revealed that DC expressed 1300-fold more ACE than did monocytes. In contrast, DC derived from acute myeloid leukemia blasts did not show an elevated level of ACE, although they acquired DC markers CD80, CD40, and CD86 upon cytokine or calcium ionophore treatment. CONCLUSIONS: ACE expression becomes the first marker to functionally distinguish DC generated from monocytes and leukemic blast cells. Given that ACE plays an important role in the hydrolysis of many peptides, as well as in the presentation of some antigens to immune cells, these data suggest that elevated ACE expression on the surface of DC is not just a reflection of the general activation of monocytes during differentiation; rather, it may be physiologically important for the functioning of these cells.