Abstract
Recent studies suggest that in addition to their common function in the regulation of thrombosis and hemostasis, platelets also contribute to tissue inflammation affecting adaptive immunity. Platelets have a number of pro-inflammatory and regulatory mediators stored in their α-granules and dense granules, which are promptly released at sites of inflammation or tissue injury. Platelet-derived mediators include cytokines (IL-1α, IL-1β, and TGFβ1), chemokines (CXCL4 and CCL3), immunomodulatory neurotransmitters (serotonin, dopamine, epinephrine, histamine, and GABA), and other low-molecular-weight mediators. In addition, activated platelets synthesize a number of lipid pro-inflammatory mediators such as platelet-activating factor and prostaglandins/thromboxanes. Notably, platelets express multiple toll-like receptors and MHC class I on their surface and store IgG in their α-granules. Platelet-derived factors are highly effective in directly or indirectly modulating the priming and effector function of various subsets of T cells. Besides secreting soluble factors, activated platelets upregulate a number of integrins, adhesion molecules, and lectins, leading to the formation of platelet–T cells aggregates. Activated platelets are able to instantly release neurotransmitters acting similar to neuronal presynaptic terminals, affecting CD4 T cells and other cells in close contact with them. The formation of platelet–T cell aggregates modulates the functions of T cells via direct cell–cell contact interactions and the local release of soluble factors including neurotransmitters. New data suggest an important role for platelets as neuronal and innate-like cells that directly recognize damage- or pathogen- associated molecular patterns and instantly communicate with T cells.
Highlights
Platelets are small non-nucleated cells around 2–3 μm in diameter, produced by megakaryocytes in the bone marrow by a budding process [1]
In addition to glycosylated components of extracellular matrix (ECM) that are recognized by platelets in the tissues, we recently found that platelets recognize specific glycolipids that are present in the detergent-resistant rigid membrane domains [ referred to as lipid rafts [40]] of postsynaptic neurons (Figure 1) and on astroglial cells that comprise the blood–brain barrier [21]
We found that during the advanced stages of human autoimmune disease multiple sclerosis, platelets become exhausted in the content of soluble factors in their granules, but upregulated integrins, lectins, and adhesion molecules effectively bind CD4 T cells, perturbing their interaction with antigenpresenting cells or endothelial cells
Summary
Platelets are small non-nucleated cells around 2–3 μm in diameter, produced by megakaryocytes in the bone marrow by a budding process [1]. The molecular mechanisms of the calcium-dependent activation of the secretory machinery and the fusion of vesicles with plasma membrane via specific docking molecules (e.g., SNAREs, VAMPs, Syntaxins) are very similar for platelets and neuronal cells and aim to release a number of neurotransmitters from platelets with the most abundant monoamine serotonin, followed by the other biogenic amines epinephrine, dopamine, and histamine [6, 8,9,10,11]. It is known that platelets release multiple soluble factors and upregulate multiple integrins and adhesion molecules during their activation, it is still not clear which activating stimuli are responsible for the release of proper factor and/ or proper surface receptor It is not clear how specific is the action of single platelet-derived factor on the proliferation and differentiation of various subsets of CD4 T cells. The classic view of the initiation of inflammation and adaptive immune response holds that the sensing by innate immune cells (macrophages, dendritic cells) of pathogen or initial tissue
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