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Articles in PresS, published online ahead of print June 20, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00104.2002
Submitted on March 6, 2002
Accepted on June 4, 2002
1 Chemical Engineering, The Johns Hopkins University, Baltimore, MD, USA
* To whom correspondence should be addressed. E-mail: konst_k{at}jhu.edu.
This study compares the kinetics, adhesion efficiency, stability and molecular requirements of polymorphonuclear leukocyte (PMN) binding to two colon adenocarcinoma cell-lines, the CD54-negative/sLex-bearing LS174T and the CD54-expressing/sLex-low HCT-8. The effects of shear rate (50-1200 sec-1), shear exposure time (10-300 sec) and shear stress (at constant shear rate) on cell-cell aggregation were assessed. The efficiency of both PMN homotypic and PMN-colon carcinoma heterotypic interactions, defined as the fraction of collisions between respective cells that result in aggregation, decreases sharply at low shear (50-200 sec-1). At higher shear, PMN homotypic efficiency remains relatively unchanged, while heterotypic efficiencies continue to decrease with PMN binding to LS174T cells being more efficient than to HCT-8 cells. The relative contributions of PMN L-selectin, CD11a and CD11b as well as their respective ligands on colon carcinomas to heterotypic aggregation are regulated by fluid shear. Furthermore, the L-selectin ligand on LS174T cells appears to be a sialylated, O-glycosylated, protease-sensitive molecule. PMN homotypic and PMN-LS174T heterotypic aggregation are primarily dependent on the intercellular contact duration, while PMN-HCT-8 binding is a function of both the intercellular contact duration and the applied force.
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