Annexin A1 is a glucocorticoid-regulated protein whose anti-inflammatory activity is carried largely by its N-terminal region. Short synthetic peptides from that region reproduce parts of the parent protein's activity while being far more tractable to make and handle, which is why Ac2-26, Ac2-12 and Ac9-25 are used as tools for studying resolution of inflammation. Ac2-12 corresponds to residues 2-12 of annexin A1 with the N-terminus acetylated. Lyngstadaas and colleagues compared the three peptides directly in cultured rat conjunctival goblet cells and found that Ac2-12 raised intracellular calcium through the formyl peptide receptor family: the response was blocked by BOC-2, an antagonist of FPR1 and FPR2/ALX. The comparison also separated the peptides from one another. Ac2-12 counter-regulated histamine stimulation only at the higher of the two concentrations tested, whereas Ac2-26 was active at the lower one, and the signalling route differed: Ac2-12 acted through beta-adrenergic receptor kinase without requiring p42/p44 MAPK/ERK1/2 or PKC, a simpler pathway than the one used by Ac2-26 or by full-length annexin A1. That distinction is the practical reason to hold Ac2-12 alongside the longer fragment rather than treating the two as interchangeable: differences between them report on which part of the N-terminal region a given response depends on. Annexin A1 mimetic peptides have been examined in several inflammation models, and the receptor family they engage is itself a target of interest. | 