α6β1 Integrin (VLA-6) Mediates Leukocyte Tether and Arrest on Laminin under Physiological Shear Flow

Polymorphonuclear leukocytes (PMN) were perfused over extracellular matrix protein substrates under laminar shear flow. Under shear below 1.5 dyn/cm2, many PMN tethered to immobilized laminin but not to fibronectin or vitronectin. Almost all the tethered PMN immediately arrested on laminin. The number of tethered PMN was mostly abrogated by mAbs to integrin α6 or β1 chains at concentrations of more than 5 μg/ml. Addition of the two mAbs together produced no further inhibition compared with each mAb alone. In contrast, none of the mAbs to α2, α3, and β4 chains showed significant inhibition, indicating that PMN tethering to laminin is mostly dependent on α6β1 integrin. The addition of 10–100 ng/ml IL-8 in the assay medium before perfusion partially reduced PMN tethering to laminin. Stimulation with IL-8 also induced detachment of some tethered PMN within 30 s. Thus, IL-8 partially weakens the adhesiveness of α6β1 integrin on PMN in flow conditions.