Induction of LFA-1-Dependent Neutrophil Rolling on ICAM-1 by Engagement of E-Selectin

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2006-03, Vol.13 (2), p.99-109
• Main Authors: CHESNUTT, BETSY C., SMITH, DAVID F., RAFFLER, NIKOLAI A., SMITH, MICHAEL L., WHITE, E. J., LEY, KLAUS
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; E-selectin; E-Selectin - metabolism; ICAM-1; Inflammation - metabolism; Intercellular Adhesion Molecule-1 - metabolism; Leukocyte Rolling - physiology; LFA-1; Lymphocyte Function-Associated Antigen-1 - metabolism; Mice; Mice, Transgenic; neutrophil; Neutrophils - cytology; Neutrophils - physiology; rolling
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1080/10739680500466376

Objective: To study rolling of mouse neutrophils on E-selectin and ICAM-1 in an ex vivo flow chamber system. Methods: The authors developed a small autoperfused flow chamber (20 × 200-μ m cross section) that allows direct visualization of cells with and without fluorescent labeling and does not require recirculation of blood. Results: Neutrophils rolled on E-selectin alone, but were unable to interact with immobilized ICAM-1. When ICAM-1 was co-immobilized with E-selectin, the number of cells that rolled was doubled, but no significant firm adhesion was observed. This phenomenon was specific for E-selectin, and no enhancement of rolling was observed when P-selectin was immobilized with ICAM-1. The increased neutrophil rolling seen on E-selectin and ICAM-1 substrates required β2 integrins. Treating mice with antibodies to the β2 integrins LFA-1 and Mac-1 showed that LFA-1 was primarily responsible for mediating rolling on ICAM-1 in this model. Increased rolling on E-selectin and ICAM-1 was significantly reduced following administration of a specific p38 mitogen-activated protein kinase (MAPK) inhibitor. Conclusion: The data show that neutrophil rolling on E-selectin leads to partial activation of LFA-1, enabling LFA-1-dependent rolling on ICAM-1. This mechanism is likely to amplify and accelerate neutrophil recruitment in inflammation.