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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1933-1942.
Prepublished online as a Blood First Edition Paper on November 17, 2005; DOI 10.1182/blood-2005-08-3137.
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Submitted August 4, 2005
Accepted October 24, 2005
Neutrophils, lymphocytes, and monocytes exhibit diverse behaviors in transendothelial and subendothelial migrations under co-culture with smooth muscle cells in disturbed flow
Cheng-Nan Chen, Shun-Fu Chang, Pei-Ling Lee, Kyle Chang, Li-Jing Chen, Shunichi Usami, Shu Chien, and Jeng-Jiann Chiu*
Institute of Life Sciences, National Defense Medical Center, and Division of Medical Engineering Research, National Health Research Institutes, Taipei, Taiwan
Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California, San Diego, CA, USA
Institute of Life Sciences, National Defense Medical Center, and Division of Medical Engineering Research, National Health Research Institutes, Taipei, Taiwan; Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan
* Corresponding author; email: jjchiu{at}nhri.org.tw.
Atherosclerosis develops at regions of arterial tree exposed to disturbed flow. The early stage of atherogenesis involves the adhesion of leukocytes (WBCs) to and their transmigration across endothelial cells (ECs), which are located in close proximity to smooth muscle cells (SMCs). We investigated the effects of EC/SMC co-culture and disturbed flow on the adhesion and transmigration of three types of WBCs [neutrophils, peripheral blood lymphocytes (PBLs), and monocytes] using our vertical-step flow (VSF) chamber, in which ECs were co-cultured with SMCs in collagen gels. Such co-culture significantly increased the adhesion and transmigration of neutrophils, PBLs, and monocytes under VSF, particularly in the reattachment area, where the rolling velocity of WBCs and their transmigration time were decreased, as compared with the other areas. Neutrophils, PBLs, and monocytes showed different subendothelial migration patterns under VSF. Their movements were more random and shorter in distance in the reattachment area. Co-culture of ECs and SMCs induced their expressions of adhesion molecules and chemokines, which contributed to the increased WBC adhesion and transmigration. Our findings provide insights into the mechanisms of WBC interaction with the vessel wall (composed of ECs and SMCs) under the complex flow environments found in regions of prevalence for atherogenesis.
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