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Microkinetics of leukocyte recruitment imaged in vascular mimetics
Author(s) -
Schaff Ulrich Y,
Xing Mengqiu,
Lin Kathleen K,
Simon Scott I
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a527-a
Subject(s) - microfluidics , biophysics , integrin , chemokine , microscope , stimulation , chemistry , materials science , nanotechnology , biomedical engineering , inflammation , cell , immunology , biology , medicine , biochemistry , pathology
A photolithography fabricated microfluidic system is presented that directs small volumes of leukocytes (~ 1 μl) in a controlled chemical environment under physiological shear stress over a vascular mimetic surface that can be imaged on an inverted microscope. Temporal and spatial gradients of the flow field and chemical concentration during operation of the microfluidics were modeled by computer fluid dynamic (CFD) simulations. CFD predicts the spatial distribution and instantaneous rolling velocity of human neutrophils (PMN) recruited to a monolayer of living cells expressing E‐selectin. Using this system, we examined the effects of IL‐8 and fMLP stimulation on PMN rolling and arrest. A threshold of stimuli was required to elicit a steady deceleration from rolling to arrest. Deceleration during sudden chemokine exposure was directly related to an increase in active conformation of β 2 ‐integrin and clustering of L‐selectin and PSGL‐1 on the PMN surface. Thus we demonstrate that the combination of low dead volume and sample consumption inherent in microfluidics is useful for classifying the critical stages of integrin conformational change on the surface of leukocytes interacting with inflamed endothelium. This research was funded by NIH R01 AI47294 and an NIH T32 training grant