title: Platelets directly enhance neutrophil transmigration in response to oxidised low-density lipoprotein.
abstract: Beyond their primary role in haemostasis and tissue repair, platelets are causally involved in the onset of inflammatory reactions, cell proliferation and immune response. Platelet activation and platelet binding to the endothelium result in release of chemokines and increased expression of adhesion molecules, which promote the recruitment of leukocytes that will eventually migrate across the endothelium into the tissue. Here, we provide the first evidence that platelets stimulated with oxidised low-density lipoprotein (oxLDL) directly enhance recruitment and transmigration of neutrophils, via cell-cell interaction. OxLDL immediately activates platelets, which then rapidly bind to neutrophils, foster their activation and facilitate transmigration through an endothelial monolayer. The observed effects of oxLDL on platelet-neutrophil aggregate (PNA) formation depend on incubation time, lipoprotein concentration and the degree of oxidative modification of LDL. PNA form within minutes following stimulation by oxLDL and remain for up to 1 h post stimulation, while native LDL is unable to induce platelet-neutrophil interactions. In the presence of acetylsalicylic acid the formation of PNA in response to oxLDL is virtually absent, and platelets fail to further enhance oxLDL-induced neutrophil transmigration. P2Y1 and P2Y12 inhibitors have less pronounced effects on PNA formation in response to oxLDL. Furthermore, we demonstrate that the PI3K pathway is essential for efficient neutrophil transmigration induced by oxLDL. Consequently, platelets enhance neutrophil transmigration in response to oxLDL and might thereby contribute essentially to the amplification of inflammatory processes within the vessel wall, which fosters the development of atherosclerosis.
authors: Institute of Physiology, Centre for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors: Sigrun
authors: S
authors: Badrnya
authors: Lynn M
authors: LM
authors: Butler
authors: Cecilia
authors: C
authors: Söderberg-Naucler
authors: Ivo
authors: I
authors: Volf
authors: Alice
authors: A
authors: Assinger
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D050197:Atherosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D019007:P-Selectin / Q000037:antagonists & inhibitors; D019869:Phosphatidylinositol 3-Kinases / Q000097:blood; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001241:Aspirin; D039481:CD11b Antigen; D002867:Chromones; D008077:Lipoproteins, LDL; D009025:Morpholines; D019007:P-Selectin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; C509295:ITGAM protein, human; C099252:oxidized low density lipoprotein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one