Differential mechanisms of microparticle transfer toB cells and monocytes: anti‐inflammatory propertiesof microparticles

Abstract

Microparticles are small vesicles released from the plasma membrane of various cell types independently of apoptosis or cell death, are transferred between cells, and carry membrane proteins from one cell to another. We have studied the mechanism of uptake of microparticles by monocytes and B cells. The transfer of microparticles to B cells was almost completely dependent on complement. Incubation of microparticles with serum resulted in opsonization of microparticles with the complement cleavage product iC3b. The subsequent transfer to B cells was mediated by the complement receptor CR2. The interaction between iC3b-opsonized microparticles and B cells reduced the activation of B cells as measured by expression of MHC class II, CD86 and CD25. In contrast, transfer of microparticles to monocytes was only partially complement dependent, but involved calcium and annexin V, and was found to change the cytokine profile of monocytes towards a reduced release of the pro-inflammatory cytokines GM-CSF and TNF-a and an increased release of the anti-inflammatory cytokine IL-10. These data show that microparticles are taken up by B cells and monocytes by different mechanisms and modulate the activation of monocytes and B cells towards an anti-inflammatory phenotype. Microparticles might be involved in counterbalancing pro-inflammatory signals arising from tissue injury or inflammation.

Microparticles released by Listeria monocytogenes-infected macrophages are required for dendritic cell-elicited protective immunity

“…We found that MHC class II deficiency in DCs significantly reduced the presentation of MPderived Lm antigen by DCs to CD4 1 T cells, evaluated by both T-cell proliferation and IFN-c production (Supplementary Figure 2). These data were consistent with a previous report demonstrating that receptors on MPs may be transferred to recipient cell surface; 31 however, these data also suggested that DCs may capture MPs through different pathways, including the membrane fusion between DCs and MPs and DC uptake and processing. Nevertheless, the detailed mechanism is worthy of further investigation.…”

Induction of Type I IFN Is a Physiological Immune Reaction to Apoptotic Cell-Derived Membrane Microparticles

“…As already pointed out for pDC function, the effects of type I IFNs include suppression of inflammatory responses through interference with TNF and IL-1b action (67,68), as well as promotion of tolerance by induction of Tr1 T regulatory cells (69), although this is less known. Both pro-and anti-inflammatory properties of MMP have been reported and are currently debated (7,(70)(71)(72). Taking into consideration that apoptotic cell debris induces TLR9-dependent IL-10 production in B lymphocytes (73) and that it was earlier demonstrated that pDC augment B cell-derived TLR9-dependent IL-10 production (32), we speculate that pDC activation by apoptotic cell-derived MMP might reveal an as-yet unappreciated role in establishing tolerogenicity in response to apoptotic cells.…”

Microvesicles: mediators of extracellular communication during cancer progression

“…For example, microvesicles derived from neutrophils are packed with cytokines that first release antiinflammatory molecules and then, at later time points, can function as pro-inflammatory mediators (Koppler et al, 2006;Mack et al, 2000). The release of metalloproteases (MMPs) from microvesicles shed by tumor cells promotes tumor invasion and metastases Ginestra et al, 1998).…”