Numerous biologically active fragments have been described that are derived from the C3 molecule. Recently, a
polypeptide (Mr 41,000) generated from the alpha chain of human
iC3b by limited proteolysis with
plasma kallikrein was shown to exhibit several
biological functions. This C3-derived cleavage product,
C3d-K, suppresses
mitogen- and
antigen-induced proliferation of human T-lymphocytes and induces
leukocytosis in rabbits. We have identified and synthesized a portion of
C3d-K that is associated with the
leukocytosis phenomenon. A nonapeptide corresponding to the amino-terminal nine residues of
C3d-K was synthesized using conventional Merrifield solid-phase
peptide chemistry; the structure of this
peptide is Thr-Leu-
Asp-Pro-Glu-
Arg-Leu-Gly-Arg (TLDPERLGR). At a final concentration of 4 X 10(-6) M, both the nonapeptide and the des-Arg octapeptide (TLDPERLG) were capable of inducing
leukocytosis in rabbits. Additionally, both
peptides enhance vascular permeability when injected in guinea pig skin. These activities are similar to those previously attributed to a C3 fragment identified as
C3e by Ghebrehiwet and Müller-Eberhard (Ghebrehiwet, B., and Müller-Eberhard, H.J. (1979) J. Immunol. 123, 616-621). We conclude that the nonapeptide TLDPERLGR represents the active center of the C3-derived
leukocytosis factors
C3e and
C3d-K. This active synthetic analogue of
C3d-K should prove valuable in elucidating the mechanism of action for
complement-dependent leukocyte mobilization in vivo.