Comparative binding of neurotrophins (NT-3, CNTF and NGF) and various cytokines to alpha 2-macroglobulin.

All the nine common cytokines in this study (including NT-3, IGF-1, CNTF and TGF-alpha) bind noncovalently, yet with different specificities and to different degrees, with both normal alpha 2-macroglobulins (alpha 2M) and monoamine-modified alpha 2M. The binding of NGF is by far the most efficient and is least affected by cationic proteins. The binding of NT-3 is slightly affected by cationic proteins but is completely blocked by NGF. The binding of TGF-alpha, TGF-beta 1, CNTF, and IL-6 is severely blocked by cationic proteins/NGF. We conclude that NGF and NT-3 appear to bind specifically in significant quantities to the same alpha 2M sites; but the other cytokines by comparison bind minimally, and primarily or entirely use nonspecific molecular interactions in their binding to alpha 2M.