CHARACTERIZATION OF THE OPIOID PEPTIDE DYNORPHIN A AS A NOVEL LIGAND FOR LEUKOCYTE INTEGRIN α M β 2 (Mac‐1)

Substantial evidence indicates that opioid peptides, including dynorphin A (Dyn A 1–17), induce leukocyte migration, their degranulation and cytokine production. The mechanisms whereby opioid peptides induce leukocyte responses are unknown. The integrin α M β 2 (Mac‐1, CD11b/CD18) is a multiligand receptor which mediates numerous reactions of leukocytes during the immune‐inflammatory response. Our recent elucidation of α M β 2 recognition specificity suggested that Dyn A contains the α M β 2 recognition motifs and can potentially interact with the receptor. In this study, we synthesized peptide libraries spanning the sequence of big dynorphin (1–31) and demonstrated that several dynorphin‐derived peptides bound recombinant 125 I‐labeled α M I‐domain, the ligand binding domain of α M β 2 . We have further shown that synthetic peptide duplicating Dyn A supported adhesion of the α M β 2 ‐expressing cells and soluble peptide inhibited adhesion. In binding to Dyn A, α M β 2 cooperated with cell surface proteoglycans since anti‐α M β 2 specific antibodies and glycosaminoglycans were required to block adhesion. The interaction of Dyn A with the α M I‐domain was activation‐independent as both the α7 helix‐truncated and helix‐extended I‐domains efficiently bound Dyn A. The results identify dynorphin as a novel ligand for α M β 2 and suggest that the interaction of α M β 2 with opioid peptides may be involved in the neuroimmune axis.