CAP37 is a multifunctional
protein isolated from human neutrophils with important implications in host defense and
inflammation. It is antimicrobial, mediates monocyte chemotaxis, and binds
endotoxin. The interaction of neutrophils with endothelial cells is a central feature in
inflammation. 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-dependent fashion. This stimulation was comparable in magnitude to that evoked by
phorbol myristate acetate. A monospecific antiserum against
CAP37 inhibited CAP37-induced PKC activity. To establish a structural basis 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 domain was distinct from the
antibiotic and
endotoxin binding domain of the molecule, which resides between
amino acids 20 and 44. These data demonstrate that
CAP37 can alter endothelial cell PKC and suggest that
CAP37 may play a role in neutrophil-endothelial interactions.