Model for SSL5 inhibition of chemokines and anaphylatoxins. (A) Chemokines and anaphylatoxins activate their target receptors through binding to both the N-terminus and the transmembrane regions, whereas peptides and lipid-derived stimuli only require the transmembrane region for activation. Some chemokines require glycosylation of the N-terminus of the target receptors for binding, whereas glycosylation is dispensable for binding of anaphylatoxins. (B) SSL5 binds all GPCRs through their glycosylation sites. However, SSL5 only inhibits cell activation by chemokines and anaphylatoxins. It thus acts on receptors that depend on their N-terminus for cell activation. Furthermore, SSL5 binds chemokines through glycans expressed on glycoproteins as PSGL-1. Thereby, it scavenges the chemokines from the chemokine receptors to prevent cell stimulation. SSL5 probably also binds chemokines through glycans presented on the chemokine receptors.