Inhibition of polymorphonuclear leukocyte activation by acetylcholinesterase

Previously we had shown that basement membrane collagen (COL IV), and specifically residues 185-203 of the non-collagenous domain of the alpha3(IV) chain, inhibits PMN activation. Since acetylcholinesterase (AchE) possesses collagenous and non-collagenous domains, we tested its effect on PMN activation. Whole AchE and the AchE recombinant catalytic subunit inhibited PMN superoxide anion (O2-) generation. AchE synthetic peptides, residues 139-154 and 252-266 of the catalytic subunit, with sequence homology to that of the alpha3(IV) peptide also inhibited O2- production by PMN. Reactive pAb and mAb to the alpha3(IV) 185-203 peptide abolished the inhibitory effect of the AchE. The data show that the non-collagenous domain of the AchE down-regulates O2- production by PMN. We suggest that this inhibitory activity may serve as a protective mechanism against PMN-mediated injury at the level of vessel wall and the neuromuscular junction.