High-shear-stress-induced activation of platelets and microparticles enhances expression of cell adhesion molecules in THP-1 and endothelial cells.
Interaction between leukocyte and endothelial cells (ECs) is essential for vascular homeostasis and competent immune-inflammatory responses in vivo. Platelet-derived microparticles (PMPs) are generated by high shear stress and may appear in diseased small arteries and arterioles in various clinical settings. In this study, we used flow cytometry and confocal laser scanning microscopy to investigate the effects of high-shear-induced platelet and microparticle activation in adhesion molecules of THP-1 and ECs. We also measured the production of some cytokines and studied cytokine mRNA from THP-1 and ECs after PMP stimulation. PMP stimulation of THP-1 cells increased CD11b, CD32, and CD33 but not CD29, CD31, and CD36. PMP stimulation of ECs increased CD54 and CD63 but not CD9, CD29, and CD31. PMPs induced interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) production by THP-1. PMPs also induced IL-8, IL-1 beta, and interleukin-6 (IL-6) production by ECs. Production was time-dependent. With RT-PCR, some cytokine mRNAs were detected in THP-1 and ECs after PMP stimulation. In relation to adhesiveness after PMP stimulation, we could clearly observe a shift in distribution not only of CD11b in THP-1 cells but also of CD54 in ECs. In addition, anti-P-selectin glycoprotein ligand-1 antibody reduced the expression of CD11b, CD32, and CD33 in THP-1 after PMP stimulation. These results suggest that high-shear-induced microparticles may contribute to the development of atherosclerosis and participate in vascular damage in inflammatory disorders.
Nomura
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Otsuka America Pharmaceutical Inc., Rockville, MD 20850, USA. fwkg4681@mb.infoweb.ne.jp
Tandon
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NN
Nakamura
T
T
Cone
J
J
Fukuhara
S
S
Kambayashi
J
J
D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D019007:P-Selectin / Q000494:pharmacology; D015539:Platelet Activation / Q000502:physiology*; D013314:Stress, Mechanical; D015854:Up-Regulation
D015703:Antigens, CD; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016207:Cytokines; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein