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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

Interaction of MPs with their target cells. (A) MPs can interact with a variety of receptors on a target cell that may or may not lead to intracellular signaling (dashed arrows). Additionally, MPs can transfer their surface components (e.g., arachidonic acid (AA), PS) and internal proteins, receptors (MHC-II, CCR5), and nucleic acids (miRNA) to the target cell by (B) membrane fusion, (C) macropinocytosis, or (D) receptor-mediated endocytosis. In the latter, MPs can engage ligands such as LFA1 (lymphocyte function-associated antigen 1), intercellular adhesion molecule 1 (ICAM1), or through binding to integrins (αvβ3 or αvβ5) by soluble proteins that recognize the PS MFGE8 (milk fat globule EGF factor 8 protein). (E) When antigen-presenting cells internalize MPs, these structures can take different pathways: (E.1) Degradation by the endocytic pathway and subsequent antigenic peptide presentation through MHC-II molecules. (E.2) Their components may be partially recycled to the surface of the target cell, leading to a gain of phenotype and/or function. (E.3) miRNA can modulate gene expression.
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fig2: Interaction of MPs with their target cells. (A) MPs can interact with a variety of receptors on a target cell that may or may not lead to intracellular signaling (dashed arrows). Additionally, MPs can transfer their surface components (e.g., arachidonic acid (AA), PS) and internal proteins, receptors (MHC-II, CCR5), and nucleic acids (miRNA) to the target cell by (B) membrane fusion, (C) macropinocytosis, or (D) receptor-mediated endocytosis. In the latter, MPs can engage ligands such as LFA1 (lymphocyte function-associated antigen 1), intercellular adhesion molecule 1 (ICAM1), or through binding to integrins (αvβ3 or αvβ5) by soluble proteins that recognize the PS MFGE8 (milk fat globule EGF factor 8 protein). (E) When antigen-presenting cells internalize MPs, these structures can take different pathways: (E.1) Degradation by the endocytic pathway and subsequent antigenic peptide presentation through MHC-II molecules. (E.2) Their components may be partially recycled to the surface of the target cell, leading to a gain of phenotype and/or function. (E.3) miRNA can modulate gene expression.

Mentions: The structural components of MPs include cell membrane receptors and/or glycoproteins in native or modified forms, nucleic acids (DNA and RNA), enzymes, cytokines, transcription factors, and in some cases secondary messengers (for further information review [20]). This diversity in MP content suggests that they can interact with different cells and can transfer their constituents to viable cells by different specific and nonspecific mechanisms of recognition such as membrane fusion, receptor-mediated endocytosis, and macropinocytosis (Figure 2) [21]. A recent report showed that at least platelets might contain mitochondrial structures and also release the mitochondria with proinflammatory effects [22], even though several references indicate that MPs lack complete signaling pathways and fully organized organelles [23]. The content of these structures confers them some functionality as agonists or antagonists of diverse biological processes involving intercellular communication wherein the modulatory effects of MPs are recognized. Therefore, it has been suggested that MPs may mediate pathological effects in several autoimmune diseases.


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

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

Interaction of MPs with their target cells. (A) MPs can interact with a variety of receptors on a target cell that may or may not lead to intracellular signaling (dashed arrows). Additionally, MPs can transfer their surface components (e.g., arachidonic acid (AA), PS) and internal proteins, receptors (MHC-II, CCR5), and nucleic acids (miRNA) to the target cell by (B) membrane fusion, (C) macropinocytosis, or (D) receptor-mediated endocytosis. In the latter, MPs can engage ligands such as LFA1 (lymphocyte function-associated antigen 1), intercellular adhesion molecule 1 (ICAM1), or through binding to integrins (αvβ3 or αvβ5) by soluble proteins that recognize the PS MFGE8 (milk fat globule EGF factor 8 protein). (E) When antigen-presenting cells internalize MPs, these structures can take different pathways: (E.1) Degradation by the endocytic pathway and subsequent antigenic peptide presentation through MHC-II molecules. (E.2) Their components may be partially recycled to the surface of the target cell, leading to a gain of phenotype and/or function. (E.3) miRNA can modulate gene expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4537755&req=5

fig2: Interaction of MPs with their target cells. (A) MPs can interact with a variety of receptors on a target cell that may or may not lead to intracellular signaling (dashed arrows). Additionally, MPs can transfer their surface components (e.g., arachidonic acid (AA), PS) and internal proteins, receptors (MHC-II, CCR5), and nucleic acids (miRNA) to the target cell by (B) membrane fusion, (C) macropinocytosis, or (D) receptor-mediated endocytosis. In the latter, MPs can engage ligands such as LFA1 (lymphocyte function-associated antigen 1), intercellular adhesion molecule 1 (ICAM1), or through binding to integrins (αvβ3 or αvβ5) by soluble proteins that recognize the PS MFGE8 (milk fat globule EGF factor 8 protein). (E) When antigen-presenting cells internalize MPs, these structures can take different pathways: (E.1) Degradation by the endocytic pathway and subsequent antigenic peptide presentation through MHC-II molecules. (E.2) Their components may be partially recycled to the surface of the target cell, leading to a gain of phenotype and/or function. (E.3) miRNA can modulate gene expression.
Mentions: The structural components of MPs include cell membrane receptors and/or glycoproteins in native or modified forms, nucleic acids (DNA and RNA), enzymes, cytokines, transcription factors, and in some cases secondary messengers (for further information review [20]). This diversity in MP content suggests that they can interact with different cells and can transfer their constituents to viable cells by different specific and nonspecific mechanisms of recognition such as membrane fusion, receptor-mediated endocytosis, and macropinocytosis (Figure 2) [21]. A recent report showed that at least platelets might contain mitochondrial structures and also release the mitochondria with proinflammatory effects [22], even though several references indicate that MPs lack complete signaling pathways and fully organized organelles [23]. The content of these structures confers them some functionality as agonists or antagonists of diverse biological processes involving intercellular communication wherein the modulatory effects of MPs are recognized. Therefore, it has been suggested that MPs may mediate pathological effects in several autoimmune diseases.

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