Effect of extracellular matrix proteins on platelet-activating factor-induced eosinophil chemotaxis

Eosinophils accumulate in tissues during various allergic inflammatory processes. Selective eosinophil recruitment is the result of orchestrated events involving cell adhesion molecules and chemoattractants. However, the exact mechanism of the regulation of integrin avidity during interstitial migration is poorly understood.

The purpose of this study was to investigate whether extracellular matrix proteins might activate human eosinophil chemotaxis and, if so, to clarify the mechanism in terms of integrin avidity.

Eosinophils were purified from the peripheral blood of healthy donors. Eosinophil migration was measured using Boyden chambers with filter membranes coated with fibronectin (Fn), vitronectin (Vn), laminin (Ln), hyaluronic acid, collagen type IV, or bovine serum albumin (BSA) overnight. Platelet-activating factor (PAF) was introduced into the lower chamber of each well. Eosinophils were placed in the upper chamber after incubation with IL-5 for 15 min. The number of eosinophils that transmigrated into the lower chamber was calculated by measuring the eosinophil peroxidase activity.

Fn, Ln and BSA enhanced PAF-induced chemotaxis of eosinophils. Inhibition experiments using blocking monoclonal antibodies showed that in the early phase of chemotaxis, Fn and Ln facilitated eosinophil chemotaxis that was mediated by alpha4 and alpha6 integrins, respectively. In the late phase of chemotaxis, BSA, but not other matrix proteins, facilitated both chemokinesis and chemotaxis that was mediated by beta2 integrin.

Our data strongly suggest that during chemotaxis, matrix proteins might activate eosinophils via binding with integrins to facilitate PAF-induced chemotaxis, and that such a mechanism might participate in allergic inflammatory processes.