Anti-C-reactive protein inhibits the calcium-dependent stage of natural killer cell activation

The studies described in this publication were designed to determine which stage of the NK lytic mechanism is inhibited by anti-C-reactive protein (CRP). Although anti-CRP prevents target cell lysis, it does not block E:T cell conjugate formation. In parallel experiments, the number of conjugates observed in the presence of anti-CRP was normal, whereas the number of target cells killed by this same group of effector cells was greatly inhibited. Since an early stage of NK-mediated lysis requires calcium, conjugates can be synchronized by incubating effector and target cells in the absence of calcium. When conjugates were formed in the absence of calcium, and anti-CRP and calcium were then added to cultures at the same time, anti-CRP inhibited maximally. Anti-CRP continued to inhibit somewhat throughout the calcium-dependent stage but did not block lysis when added after the completion of calcium requiring events. Events that are blocked by anti-CRP must be required for the generation of NK cytotoxic factor because anti-CRP blocks the production of this factor. Once generated, however, anti-CRP does not block the activity of NK cytotoxic factor. This evidence indicates that anti-CRP blocks NK-mediated lysis at the calcium dependent stage of lysis. Events that follow this stage in the lytic process are also inhibited.