On the origin of microparticles: From "platelet dust" to mediators of intercellular communication

Abstract

Microparticles are submicron vesicles shed from a variety of cells. Peter Wolf first identified microparticles in the midst of ongoing blood coagulation research in 1967 as a product of platelets. He termed them platelet dust. Although initially thought to be useless cellular trash, decades of research focused on the tiny vesicles have defined their roles as participators in coagulation, cellular signaling, vascular injury, and homeostasis. The purpose of this review is to highlight the science leading up to the discovery of microparticles, feature discoveries made by key contributors to the field of microparticle research, and discuss their positive and negative impact on the pulmonary circulation.

Keywords: coagulation; microparticles; pulmonary circulation.

Figure 1

Microparticles isolated by ultracentrifugation and analyzed by electron microscopy. (A) Microparticles secreted into the media by pulmonary microvascular endothelial cells exhibit some ultrastructural heterogeneity as seen by the differences in the electron dense center and membrane. Scale bar = 500 nm (B) Single microparticle isolated as above. Scale bar = 200 nm.

Figure 2

Mechanisms of microparticle generation. The mechanisms of microparticle generation are multifaceted. Many of the current identified mechanisms are calcium-dependent, and all mechanisms to date depend on some part of the complex intracellular or membrane cytoskeleton.

Figure 3

Contents and targeting of microparticles. (A) Microparticles contain several intracellular and membrane components hijacked from their parent cell. The intracellular components include transcription factors, microRNAs, mRNAs, and proteins. The membrane components include fatty acids, receptors, integral membranes, and receptors. (B) At least two mechanisms of targeting of microparticles to effector cells have been suggested. The first involves a membrane fusion or endocytosis in which the constituents of the microparticle are “emptied” into the cytoplasm of the recipient cells. The second involves interaction of the microparticle with a membrane receptor or integrin to stimulate cellular signaling events.