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β 2 ‐Integrins mediate stable adhesion in collisional interactions between neutrophils and ICAM‐1‐expressing cells
Author(s) -
Lynam Eric,
Sklar Larry A.,
Taylor Andrew D.,
Neelamegham Sriram,
Edwards Bruce S.,
Smith C. Wayne,
Simon Scott I.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.5.622
Subject(s) - integrin , biology , icam 1 , adhesion , microbiology and biotechnology , cell adhesion , intercellular adhesion molecule 1 , cell adhesion molecule , immunology , receptor , cell , genetics , chemistry , organic chemistry
The aggregation of human neutrophils in suspension has features that are analogous to their attachment to activated endothelium in that both involve selectin and β 2 ‐integrin adhesion receptors. For the collisional interaction that forms neutrophil aggregates in suspension, there is a tethering step in which L‐selectin on neutrophils binds PSGL‐1. At relatively low shear rates (100–200 s ‐1 ) firm adhesion is mediated in equal measure by LFA‐1 binding to ICAM‐3, and Mac‐1 binding to an as yet undefined ligand. In this report we used a mouse melanoma cell line expressing an estimated 700,000 ICAM‐1 (CD54) to examine the relative roles of LFA‐1 and Mac‐1 over the kinetics of heterotypic cell adhesion in shear mixed suspensions. Neither heterotypic nor homotypic neutrophil aggregates formed with application of shear alone. However, the rate of aggregation peaked within seconds of chemotactic stimulation. In contrast to homotypic aggregation, neither L‐selectin nor its O‐glycoprotein ligands on neutrophils contributed to heterotypic adhesion. Adhesion was inhibited in a dose‐dependent manner as ICAM‐1 was titrated with blocking mAb. A direct interaction between LFA‐1 and ICAM‐1 was preferred over the first minute of stimulation, whereas at later times adhesion was supported equally by Mac‐1. Activation with MnCl 2 also favored participation of the constitutively expressed LFA‐1. Application of defined shear in a cone and plate viscometer showed that adhesion to the ICAM‐1 cells decreased from a maximum level to baseline as shear rate increased up to 400 s ‐1 in a manner typical of integrin adhesion alone. In contrast, homotypic aggregation supported by the transition from selectin to integrin binding exhibited an increase in efficiency up to 800 s ‐1 . The pathophysiological significance of receptor site density and duration of contact in collisional interactions relevant to leukocyte recruitment compared to leukocyte‐endothelial cell interactions on surfaces is discussed. J. Leukoc. Biol. 64: 622–630; 1998.