title: Selective induction of anti-inflammatory monocyte-platelet aggregates in a model of pulsatile blood flow at low shear rates.
abstract: In patients with cardiovascular abnormalities or immunological disorders, an increased number of circulating leukocyte-platelet aggregates is observed. Leukocyte-platelet aggregates play an essential role in linking the hemostatic and immune systems. High shear stress and pro-coagulant and pro-inflammatory stimulants are known to activate platelets and promote the formation of aggregates. Pulsatile blood flow under low shear stress can also induce platelet activation in comparatively mild conditions. However, the effect of such events on leukocyte-platelet aggregates has not yet been investigated. To determine whether low shear stress affects the formation of aggregates, we established a simple "inverting rotation" method of inducing periodic changes in the direction of blood flow in combination with low shear stress. We demonstrated that after the inverting rotation treatment for 10-20 min more than 70% of monocytes selectively aggregated with platelets. The formation of monocyte-platelet complexes was inhibited by an anti-CD162 (PSGL-1) monoclonal antibody or a Ca(2+) chelator. The phagocytic activity of monocytes was augmented by inverting rotation, whereas phagocytosis mediated by granulocytes remained unaffected. Interestingly, the formation of monocyte-platelet complexes suppressed the production of pro-inflammatory cytokines such as interleukin (IL)-1β. At the same time, monocyte-platelet complexes augmented the expression of the anti-inflammatory cytokine IL-10. Our results suggest that platelet-bound monocytes show an anti-inflammatory phenotype under low shear stress conditions. Thus, our method provided new insights into the mechanisms of monocyte-platelet aggregate formation and regulation.
authors.affiliation: a Department of Environmental and Preventive Medicine , Hyogo College of Medicine , Nishinomiya , Japan.|b Department of Immunology, Faculty of Medicine , Yamagata University , Yamagata , Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takeda
authors.affiliation: a Department of Environmental and Preventive Medicine , Hyogo College of Medicine , Nishinomiya , Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Marumo
authors.affiliation: b Department of Immunology, Faculty of Medicine , Yamagata University , Yamagata , Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nara
authors.affiliation: c Department of Bio-Systems Engineering , Graduate School of Science and Engineering, Yamagata University , Yamagata , Japan.
authors.forename: Zhong-Gang
authors.initials: ZG
authors.lastname: Feng
authors.affiliation: b Department of Immunology, Faculty of Medicine , Yamagata University , Yamagata , Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Asao
authors.affiliation: a Department of Environmental and Preventive Medicine , Hyogo College of Medicine , Nishinomiya , Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Wakabayashi
mesh_terms: D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002449:Cell Aggregation; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006439:Hemodynamics; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis; D015539:Platelet Activation; D010973:Platelet Adhesiveness
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D002118:Calcium
keywords: Inflammatory cytokine; PSGL-1; leukocyte-platelet aggregates; low shear stress; monocytes