Sulfonamide inhibitors of α 2 β 1 integrin reveal the essential role of collagen receptors in in vivo models of inflammation

Small molecule inhibitors of α 2 β 1 integrin, a major cellular collagen receptor, have been reported to inhibit platelet function, kidney injury, and angiogenesis. Since α 2 β 1 integrin is abundantly expressed on various inflammation‐associated cells, we tested whether recently developed α 2 β 1 blocking sulfonamides have anti‐inflammatory properties. Integrin α 2 β 1 inhibitors were shown to reduce the signs of inflammation in arachidonic acid‐induced ear edema, PAF stimulated air pouch, ovalbumin‐induced skin hypersensitivity, adjuvant arthritis, and collagen‐induced arthritis. Thus, these sulfonamides are potential drugs for acute and allergic inflammation, hypersensitivity, and arthritis. One sulfonamide with potent anti‐inflammatory activity has previously been reported to be selective for activated integrins, but not to inhibit platelet function. Thus, the experiments also revealed fundamental differences in the action of nonactivated and activated α 2 β 1 integrins in inflammation when compared to thrombosis.