Curvature of Synthetic and Natural Surfaces Is an Important Target Feature in Classical Pathway Complement Activation

Thebinding ofAbs to microbial surfaces followed by complement activation constitutes animportant line of defense against infections. In this study, we have investigated the relationship between complement activation and the binding ofhuman IgMAbs to surfaces with different curvatures. IgM Abs to dextran were shown to activate complement potently on dextran-coated particles having a diameter around 250 nm, whereas larger (600 nm) particles were less potent activators. This selectivity regarding particle dimension was also found for complement activation by colloidal substances of microbial origin.Peptidoglycan (PGN) is the major chemical component in the cell wall of Gram-positive bacteria. Fragments of purifiedPGNwith sizes of∼100nmpromoted complement activation effectively through the classical pathway. By contrast, larger or smaller fragments of PGN did not activate complement strongly. A careful analysis of PGN fragments released during planctonic growth of Staphylococcus aureus showed that these include curvatures that would permit strong IgM-mediated complement activation, whereas the curvature of intact cells would be less effective for such activation. Consistently, we found that the suspended PGN fragments were strong activators of complement through the classical pathway.We suggest that these fragments act as decoy targets for complement activation, providing protection for S. aureus against the host immune response to infection.