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Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses.

Burbano C, Rojas M, Vásquez G, Castaño D - Mediators Inflamm. (2015)

Bottom Line: However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them.They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells.This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

View Article: PubMed Central - PubMed

Affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia ; Unidad de Citometría de Flujo, Sede de Investigación Universitaria, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.

ABSTRACT
Microparticles (MPs) are induced during apoptosis, cell activation, and even "spontaneous" release. Initially MPs were considered to be inert cellular products with no biological function. However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them. They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells. MPs interact with their target cells through different mechanisms: membrane fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs remain in the extracellular milieu, they undergo modifications such as citrullination, glycosylation, and partial proteolysis, among others, becoming a source of neoantigens. In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), reports indicated elevated levels of MPs with different composition, content, and effects compared with those isolated from healthy individuals. MPs can also form immune complexes amplifying the proinflammatory response and tissue damage. Their early detection and characterization could facilitate an appropriate diagnosis optimizing the pharmacological strategies, in different diseases including cancer, infection, and autoimmunity. This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

No MeSH data available.


Related in: MedlinePlus

Role of MPs in SLE. MPs can interact with B cells (LB) (a) during ontogeny-induced apoptosis (clonal deletion), secondary rearrangement, or BCR edition in cells whose BCRs recognize DNA with high affinity. (b) At the lymphoid organ level, MPs can also bind to an autoreactive BCR and induce anergy of LB or alternatively be endocytosed by these cells and induce a second signal through TLR9 and TLR7 by the DNA and RNA present on these structures. These recognition activate and differentiate B cells into plasma cells able to produce autoantibodies. (c) MPs can be internalized by plasmacytoid dendritic cells (pDCs) and through the recognition of nucleic acids produce type I IFNs and other cytokines such as IL-6. (d) MPs might compete with ACs to bind PS receptors on monocytes and macrophages (Mo/MΦ), which seem to contribute to the lower uptake of ACs observed in these patients. In addition, MPs can be a major source of autoantigens in SLE with the consequent generation of ICs; all this could eventually (1) produce and maintain the inflammatory immune response and (2) promote the damage of different tissues and organs in patients with SLE due to the exacerbated inflammatory process.
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fig3: Role of MPs in SLE. MPs can interact with B cells (LB) (a) during ontogeny-induced apoptosis (clonal deletion), secondary rearrangement, or BCR edition in cells whose BCRs recognize DNA with high affinity. (b) At the lymphoid organ level, MPs can also bind to an autoreactive BCR and induce anergy of LB or alternatively be endocytosed by these cells and induce a second signal through TLR9 and TLR7 by the DNA and RNA present on these structures. These recognition activate and differentiate B cells into plasma cells able to produce autoantibodies. (c) MPs can be internalized by plasmacytoid dendritic cells (pDCs) and through the recognition of nucleic acids produce type I IFNs and other cytokines such as IL-6. (d) MPs might compete with ACs to bind PS receptors on monocytes and macrophages (Mo/MΦ), which seem to contribute to the lower uptake of ACs observed in these patients. In addition, MPs can be a major source of autoantigens in SLE with the consequent generation of ICs; all this could eventually (1) produce and maintain the inflammatory immune response and (2) promote the damage of different tissues and organs in patients with SLE due to the exacerbated inflammatory process.

Mentions: Pisetsky and Lipsky [9] proposed an interesting model of the pathogenesis of MPs in SLE based on their own results and those from other authors (Figure 3). MPs that contain DNA and RNA can behave as self-adjuvants and increase tolerance of immature B-lymphocytes and break the tolerance of mature B cells. Immature B cells that recognize DNA on MPs with high avidity can be negatively selected. In contrast, self-reactive B lymphocytes that escape from central tolerance mechanisms can recognize and endocytose MPs through their BCR at the periphery. This might favor contact of the nucleic acids present on MPs with endosomal TLR9 in B lymphocytes. This interaction may trigger their activation and differentiation into plasma cells with the consequent production of autoantibodies in a manner independent of T lymphocytes.


Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses.

Burbano C, Rojas M, Vásquez G, Castaño D - Mediators Inflamm. (2015)

Role of MPs in SLE. MPs can interact with B cells (LB) (a) during ontogeny-induced apoptosis (clonal deletion), secondary rearrangement, or BCR edition in cells whose BCRs recognize DNA with high affinity. (b) At the lymphoid organ level, MPs can also bind to an autoreactive BCR and induce anergy of LB or alternatively be endocytosed by these cells and induce a second signal through TLR9 and TLR7 by the DNA and RNA present on these structures. These recognition activate and differentiate B cells into plasma cells able to produce autoantibodies. (c) MPs can be internalized by plasmacytoid dendritic cells (pDCs) and through the recognition of nucleic acids produce type I IFNs and other cytokines such as IL-6. (d) MPs might compete with ACs to bind PS receptors on monocytes and macrophages (Mo/MΦ), which seem to contribute to the lower uptake of ACs observed in these patients. In addition, MPs can be a major source of autoantigens in SLE with the consequent generation of ICs; all this could eventually (1) produce and maintain the inflammatory immune response and (2) promote the damage of different tissues and organs in patients with SLE due to the exacerbated inflammatory process.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537755&req=5

fig3: Role of MPs in SLE. MPs can interact with B cells (LB) (a) during ontogeny-induced apoptosis (clonal deletion), secondary rearrangement, or BCR edition in cells whose BCRs recognize DNA with high affinity. (b) At the lymphoid organ level, MPs can also bind to an autoreactive BCR and induce anergy of LB or alternatively be endocytosed by these cells and induce a second signal through TLR9 and TLR7 by the DNA and RNA present on these structures. These recognition activate and differentiate B cells into plasma cells able to produce autoantibodies. (c) MPs can be internalized by plasmacytoid dendritic cells (pDCs) and through the recognition of nucleic acids produce type I IFNs and other cytokines such as IL-6. (d) MPs might compete with ACs to bind PS receptors on monocytes and macrophages (Mo/MΦ), which seem to contribute to the lower uptake of ACs observed in these patients. In addition, MPs can be a major source of autoantigens in SLE with the consequent generation of ICs; all this could eventually (1) produce and maintain the inflammatory immune response and (2) promote the damage of different tissues and organs in patients with SLE due to the exacerbated inflammatory process.
Mentions: Pisetsky and Lipsky [9] proposed an interesting model of the pathogenesis of MPs in SLE based on their own results and those from other authors (Figure 3). MPs that contain DNA and RNA can behave as self-adjuvants and increase tolerance of immature B-lymphocytes and break the tolerance of mature B cells. Immature B cells that recognize DNA on MPs with high avidity can be negatively selected. In contrast, self-reactive B lymphocytes that escape from central tolerance mechanisms can recognize and endocytose MPs through their BCR at the periphery. This might favor contact of the nucleic acids present on MPs with endosomal TLR9 in B lymphocytes. This interaction may trigger their activation and differentiation into plasma cells with the consequent production of autoantibodies in a manner independent of T lymphocytes.

Bottom Line: However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them.They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells.This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

View Article: PubMed Central - PubMed

Affiliation: Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia ; Unidad de Citometría de Flujo, Sede de Investigación Universitaria, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín, Colombia.

ABSTRACT
Microparticles (MPs) are induced during apoptosis, cell activation, and even "spontaneous" release. Initially MPs were considered to be inert cellular products with no biological function. However, an extensive research and functional characterization have shown that the molecular composition and the effects of MPs depend upon the cellular background and the mechanism inducing them. They possess a wide spectrum of biological effects on intercellular communication by transferring different molecules able to modulate other cells. MPs interact with their target cells through different mechanisms: membrane fusion, macropinocytosis, and receptor-mediated endocytosis. However, when MPs remain in the extracellular milieu, they undergo modifications such as citrullination, glycosylation, and partial proteolysis, among others, becoming a source of neoantigens. In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), reports indicated elevated levels of MPs with different composition, content, and effects compared with those isolated from healthy individuals. MPs can also form immune complexes amplifying the proinflammatory response and tissue damage. Their early detection and characterization could facilitate an appropriate diagnosis optimizing the pharmacological strategies, in different diseases including cancer, infection, and autoimmunity. This review focuses on the current knowledge about MPs and their involvement in the immunopathogenesis of SLE and RA.

No MeSH data available.


Related in: MedlinePlus