Substance P-induced contraction of airway smooth muscle in young and adult rabbits. Effects of epithelium removal and neutral endopeptidase inhibition.

principle, lead to depletion of VIP in the airways and abnormalities characteristic of asthma. To examine whether catalytic antibodies can evolve over the normal course of antibody affinity maturation, we prepared monoclonal antibodies by immunization with a VIP-carrier protein conjugate. One of these antibodies hydrolyzed VIP with Km (Michaelis-Menten constant) 0.34 nM and turnover 8X10-4/min. The purified, recombinant light chain of this antibody hydrolyzed VIP efficiently. An enzyme-like active site that may account for the catalytic activity of the antibody was identified by molecular modeling. Recombinant single chain Fv displayed binding VIP-affinity identical to that of the parent antibody. We concluded that a catalytic function can evolve naturally in antibodies, resulting, presumably, from the extraordinary rate of sequence diversification in these molecules. In principle, catalysis by antibodies may be an important mediator of autoimmune dysfunction. Moreover, the isolation of substrate-specific catalytic antibodies offers the possibility of selective degradation of clinically important polypeptide targets for therapeutic purposes.