THE ALPHA(4)BETA(1) INTEGRIN CAN MEDIATE LEUKOCYTE ADHESION TO CASEINAND DENATURED PROTEIN SUBSTRATES

An understanding of the binding specificity of leukocyte integrins is important to determine the range of ligands that interact with these r eceptors during inflammatory processes. In this study we show that the alpha(4) beta(1) integrin can interact with casein and denatured albu min and promote leukocyte adhesion through these interactions. This wa s demonstrated with the use of blocking antibodies directed to alpha(4 ) beta(1) and peptide adhesion competitors containing the alpha(4) bet a(1) binding tripeptide, Leu-Asp-Val (LDV). Consistent with this data, the adhesion is completely divalent cation-dependent and is stimulate d by known activators of leukocyte integrin function, namely phorbol e ster and the beta(1) integrin activating antibody, 8A2. It is interest ing to note that neither bovine alpha-casein or human albumin contain an LDV site (present in the CS-1 site of alternatively spliced fibrone ctin) or an IDS site (present in VCAM-1) yet they promote adhesion thr ough this integrin. Furthermore, alpha(4) beta(1) directly binds to Se pharose columns containing casein, casein fragments, or denatured albu min but does not bind columns containing native albumin. These data su ggest that the binding specificity for the alpha(4) beta(1) integrin i s considerably broader than previously realized. This work has implica tions for how subsets of leukocytes may interact with damaged proteins during tissue injury and inflammation.