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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 RA. The high concentrations of MPs from different leukocyte populations reported in the synovial fluid from RA patients must be citrullinated and form ICs with anti-CCP antibodies and RF autoantibodies. These complex structures could be recognized by Mo/MΦ through isotype-specific Fc receptors (FcγR and FcμR) and induce the production of proinflammatory cytokines such as TNF-alpha, IL-6, and the chemokines CCL2, CCL3, and RANTES. These soluble factors participate in the systemic inflammation in the synovium and the destructive changes observed in the joints of RA patients. IL-6 is also involved in the induction of plasma cells (PCs) producing autoantibodies.
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fig4: Role of MPs in RA. The high concentrations of MPs from different leukocyte populations reported in the synovial fluid from RA patients must be citrullinated and form ICs with anti-CCP antibodies and RF autoantibodies. These complex structures could be recognized by Mo/MΦ through isotype-specific Fc receptors (FcγR and FcμR) and induce the production of proinflammatory cytokines such as TNF-alpha, IL-6, and the chemokines CCL2, CCL3, and RANTES. These soluble factors participate in the systemic inflammation in the synovium and the destructive changes observed in the joints of RA patients. IL-6 is also involved in the induction of plasma cells (PCs) producing autoantibodies.

Mentions: TNF-α has been identified as a key component of RA with multifunctional effects associated with inflammation and joint destruction [100]. The efficacy of anti-TNF-α treatment in RA has led to extensive research about the mechanisms that regulate its production in this disease. Reports indicate that 50 percent of RA patients are positive for anti-CCPs and circulating ICs formed by citrullinated fibrinogen [101]. These ICs induce the production of TNF-α in vitro by macrophages obtained from normal controls in a dose-dependent manner; this production was found to be inhibited by blockade of FcγRIIa but not FcγRI or FcγRIII [102]. In addition, the simultaneous binding of ICs containing citrullinated fibrinogen by FcγR and TLR4 induces even more TNF-α production by macrophages from healthy subjects [103]. Because there are increased levels of MPs forming ICs that depend on citrullinated antigens in the synovial fluid of RA patients [12], we hypothesize that the systemic inflammatory response and intrinsic activation of monocytes and synovial macrophages in RA patients may be partially explained by the recognition of these structures through FcγRs and complement receptors. However, the potential involvement of other receptors should be noted such as FcμR (TOSO), which can recognize the FR (IgM isotype) on MPs (95) if this antibody is present in these membrane structures. Therefore, we propose that MPs could be the major source of circulating ICs in RA patients, which would lead to mononuclear phagocyte activation and the secretion of different mediators such as TNF-α, IL-6, and chemokines (CCL2, CCL3, and RANTES) that amplify the local and systemic inflammatory responses (Figure 4).


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 RA. The high concentrations of MPs from different leukocyte populations reported in the synovial fluid from RA patients must be citrullinated and form ICs with anti-CCP antibodies and RF autoantibodies. These complex structures could be recognized by Mo/MΦ through isotype-specific Fc receptors (FcγR and FcμR) and induce the production of proinflammatory cytokines such as TNF-alpha, IL-6, and the chemokines CCL2, CCL3, and RANTES. These soluble factors participate in the systemic inflammation in the synovium and the destructive changes observed in the joints of RA patients. IL-6 is also involved in the induction of plasma cells (PCs) producing autoantibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Role of MPs in RA. The high concentrations of MPs from different leukocyte populations reported in the synovial fluid from RA patients must be citrullinated and form ICs with anti-CCP antibodies and RF autoantibodies. These complex structures could be recognized by Mo/MΦ through isotype-specific Fc receptors (FcγR and FcμR) and induce the production of proinflammatory cytokines such as TNF-alpha, IL-6, and the chemokines CCL2, CCL3, and RANTES. These soluble factors participate in the systemic inflammation in the synovium and the destructive changes observed in the joints of RA patients. IL-6 is also involved in the induction of plasma cells (PCs) producing autoantibodies.
Mentions: TNF-α has been identified as a key component of RA with multifunctional effects associated with inflammation and joint destruction [100]. The efficacy of anti-TNF-α treatment in RA has led to extensive research about the mechanisms that regulate its production in this disease. Reports indicate that 50 percent of RA patients are positive for anti-CCPs and circulating ICs formed by citrullinated fibrinogen [101]. These ICs induce the production of TNF-α in vitro by macrophages obtained from normal controls in a dose-dependent manner; this production was found to be inhibited by blockade of FcγRIIa but not FcγRI or FcγRIII [102]. In addition, the simultaneous binding of ICs containing citrullinated fibrinogen by FcγR and TLR4 induces even more TNF-α production by macrophages from healthy subjects [103]. Because there are increased levels of MPs forming ICs that depend on citrullinated antigens in the synovial fluid of RA patients [12], we hypothesize that the systemic inflammatory response and intrinsic activation of monocytes and synovial macrophages in RA patients may be partially explained by the recognition of these structures through FcγRs and complement receptors. However, the potential involvement of other receptors should be noted such as FcμR (TOSO), which can recognize the FR (IgM isotype) on MPs (95) if this antibody is present in these membrane structures. Therefore, we propose that MPs could be the major source of circulating ICs in RA patients, which would lead to mononuclear phagocyte activation and the secretion of different mediators such as TNF-α, IL-6, and chemokines (CCL2, CCL3, and RANTES) that amplify the local and systemic inflammatory responses (Figure 4).

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