Trafficking of leukocytes and their local activity profile are of pivotal importance for many (patho)physiological processes. Fittingly, microenvironments are complex by nature, with multiple mediators originating from diverse cell types and playing roles in an intimately regulated manner. To dissect aspects of this complexity, effectors are initially identified and structurally characterized, thus prompting familial classification and establishing foci of research activity. In this regard,
chemokines present themselves as role models to illustrate the diversification and fine-tuning of inflammatory processes. This in turn discloses the interplay among
chemokines, their cell receptors and cognate
glycosaminoglycans, as well as their capacity to engage in new molecular interactions that form hetero-oligomers between themselves and other classes of effector molecules. The growing realization of versatility of adhesion/growth-regulatory
galectins that bind to
glycans and
proteins and their presence at sites of
inflammation led to testing the hypothesis that
chemokines and
galectins can interact with each other by
protein-
protein interactions. In this review, we present some background on
chemokines and
galectins, as well as experimental validation of this
chemokine-
galectin heterodimer concept exemplified with CXCL12 and
galectin-3 as proof-of-principle, as well as sketch out some emerging perspectives in this arena.