CAP37, A NEUTROPHIL GRANULE-DERIVED PROTEIN STIMULATES PROTEIN-KINASE-C ACTIVITY IN ENDOTHELIAL-CELLS

CAP37 is a multifunctional protein isolated from human neutrophils wit h important implications in host defense and inflammation. It is antim icrobial, mediates monocyte chemotaxis, and binds endotoxin. The inter action of neutrophils with endothelial cells is a central feature in i nflammation. The object of this study was to determine whether CAP37, a neutrophil-derived protein, could regulate vascular endothelial cell protein kinase C (PKC), an important signaling enzyme. We found that CAP37 stimulated endothelial PKC activity in both a time-and dose-depe ndent fashion. This stimulation was comparable in magnitude to that ev oked by phorbol myristate acetate. A monospecific antiserum against CA P37 inhibited CAP37-induced PKC activity. To establish a structural ba sis for this activity, overlapping peptides, based on the sequence of native CAP37 were synthesized. Maximum PKC stimulation was evoked by a peptide corresponding to amino acids 95-122 of native CAP37. This dom ain was distinct from the antibiotic and endotoxin binding domain of t he molecule, which resides between amino acids 20 and 44. These data d emonstrate that CAP37 can alter endothelial cell PKC and suggest that CAP37 may play a role in neutrophil-endothelial interactions.