Functional alpha(4)-integrin: A newly identified pathway of neutrophil recruitment in critically ill septic patients

Using a novel flow chamber assay system and whole blood, we show that leuko cytes from septic individuals have a four-fold elevation of adhesion, but n ot rolling, on a P-seIectin/beta (2)-integrin substrate. Most leukocytes fr om septic patients (but not healthy controls) that bound vascular cell adhe sion molecule 1 (VCAM-1) were neutrophils. All adhesion was inhibited with an antibody specific for the VCAM-1 ligand alpha (4)-integrin. The alpha (4 )-integrin was present on neutrophils from septic patients but not on neutr ophils from patients with localized bacterial infections. The plasma milieu of septic patients was sufficient to induce neutrophils from healthy subje cts to bind VCAM-1 under flow conditions. This is the first description of alpha (4)-integrin/VCAM-1 pathway of neutrophil recruitment in human diseas e. This pathway may provide a new therapeutic target to reduce inappropriat e neutrophil adhesion without altering the normal yet critical beta (2)-int egrin-mediated adhesive function of neutrophils.