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Antwi-Baffour, Samuel (2010) Plasma membrane-derived vesicles: their role in the terminal differentiation of monocytes and in inhibiting the phagocytosis of apoptotic cells. Doctoral thesis, London Metropolitan University.
Plasma Membrane-derived Vesicles (PMVs) are membrane-coated vesicles of diameter 0.1 to 1 μm, carrying various proteins inherent in their parental cells. PMVs are released when cells undergo activation/apoptosis via blebbing and shedding and have a function in intercellular communication. Exposition of phosphotidylserine (PS) on the outer membrane leaflet that mark them as a biologically distinct entity could explain a role for PMVs in phagocytosis and thrombosis.
There is currently a large amount of variation between researchers with regards to characterisation of PMVs as a result of less or no standardization in the pre and post analytical steps employed in PMV work. Efforts are being made to combat these issues, but still, proper standardization of analytical procedures is yet to be achieved. The purpose of this work is to be able to properly analyse, categorise and characterise PMVs to help lay the groundwork for PMV testing in clinical settings. We have examined the role of PMVs, in the differentiation of HL-60 promonocytes.
The myeloid differentiating agents ATRA, PMA and histamine, which inhibit promonocyte proliferation, induced an intracellular Ca2 +-mediated PMV (as opposed to exosome) release from HL-60 promonocytes. These PMVs caused HL-60 cells to enter GO/G 1 cell cycle arrest and induce terminal monocyte-to-macrophage differentiation through TGF-J31 mediation.
Patients with inflammatory diseases such as SLE show increased PMV levels in the plasma, accompanied by persistent apoptosis and defective clearance, which correlates with the disease activity. Although still unclear, impaired clearance of apoptotic cells (ACs) may represent a mechanism for the development or enhancement of SLE. We found that PMVs dose dependently inhibit the phagocytosis of ACs by competing for the PS receptor on macrophages via which ACs are phagocytosed. PMVs can therefore modulate phagocytosis of ACs and may playa role in the aetiology of autoimmune diseases, in particular SLE.
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