Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV

Abstract

We postulate that both PMP and MegaMP may play a novel and important role in spreading HIV-1 infection by transferring the CXCR4 co-receptor to CD4+/CXCR4-null cells.

Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer

“…Not only were significantly more metastatic foci found in the lungs of mice injected with PMV-covered LCC cells, but also there were significantly more LCC cells detected in the bone marrow cavities of these mice. As PMV have been shown to transfer G-protein-coupled 7-transmembrane-span receptors such as CXCR4 onto the surface of target cells, 11,12,14 it is reasonable to suggest that LCC cells pre-incubated with PMV acquired CXCR4 on their surface and responded to the SDF-1-rich environment of the bone marrow. Previously, we reported that all 5 human lung cancer cell lines studied here do not express the CXCR4 receptor 33 ; however, as shown in other models, cells can be rendered CXCR4-positive by PMV, and CXCR4 transferred by PMV may be functional as a coreceptor for HIV entry 14 or tether PMV ϩ cells to SDF-1 exposed on endothelium.…”

“…As PMV have been shown to transfer G-protein-coupled 7-transmembrane-span receptors such as CXCR4 onto the surface of target cells, 11,12,14 it is reasonable to suggest that LCC cells pre-incubated with PMV acquired CXCR4 on their surface and responded to the SDF-1-rich environment of the bone marrow. Previously, we reported that all 5 human lung cancer cell lines studied here do not express the CXCR4 receptor 33 ; however, as shown in other models, cells can be rendered CXCR4-positive by PMV, and CXCR4 transferred by PMV may be functional as a coreceptor for HIV entry 14 or tether PMV ϩ cells to SDF-1 exposed on endothelium. 12 Although it is apparent that PMV contain components that alone or in combination are responsible for the various effects observed, the particular components responsible remain to be elucidated.…”

“…11,12,14 Hence, we wished to determine whether the same was true for lung cancer cells. All 5 human lung cancer cell lines studied became CD41-positive when pre-incubated with PMV (Fig.…”

“…7,8 Recently, we and others have postulated that MV are important signaling molecules in intercellular crosstalk. [11][12][13][14] This communication between cells may perhaps have developed very early in the course of eukaryocytic evolution, before soluble mediators emerged.…”

“…11,12 They may also play a role in HIV infection; for example, we have reported that PMV transfer the HIV-entry co-receptor CXCR4 to the surface of CXCR4-negative cells, and even infectious HIV particles inside PMV may enter cells in a "Trojan horse" type of mechanism. 14,25 PMV released by activated platelets are of 2 types, cell-surface membrane vesicles and exosomes, both of which can be isolated by differential gradient centrifugation. 7 The PMV that are released from surface membranes are generated in a calcium flux-calpaindependent manner and are relatively large (100 nm-1 m).…”