Inhibition of Haemagglutination by Benzylpenicillin adsorbed on Erythrocytes

Abstract

INVESTIGATIONS of the inhibition of haemagglutination have demonstrated the role of the penicilloyl group as the major antigenic determinant¹. Coating of erythrocytes either with benzylpenicillin or with penicillenic acid leads to covalent bonding of penicilloyl haptene groups either by irreversible reaction of penicillenic acid with lysine ɛ-amine groups or by coupling involving the direct addition of the β-lactam carbonyl to lysine ammo residues of membranous proteins. According to Levine² the former mechanism is more likely. Combination of penicillenic acid through disulphide linkages, as reported by De Week and Eisen³, has been attributed by Levine and Ovary⁴ to small numbers of penicilloyl groups in the penicillenate conjugates. However, such groups were not detected by De Weck¹ and no cross-reactions were observed with anti-penicilloyl antisera. Occasional human sera are encountered in which inhibition is more effective with other degradation compounds of benzylpenicillin, namely, penamaldate, penilloate, penicillenate and penicilloate. Consequently, it is probable that other haptene specificities may be involved in the haemagglutination system, but their role is so far unestablished. In general, unaltered benzylpenicillin is a less effective inhibitor at equimolar concentrations. Because of this and the failure of benzylpenicillin to form stable covalent bonds with proteins it has been considered unlikely that the unaltered compound can function as an effective haptene.