A synthetic nonapeptide corresponding to the NH2-terminal sequence of C3d-K causes leukocytosis in rabbits.
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.
D000595:Amino Acid Sequence; D000706:Anaphylatoxins; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003176:Complement C3 / Q000032:analysis; D015926:Complement C3a; D003179:Complement C3b; D015933:Complement C3d; D003182:Complement C5; D015936:Complement C5a; D007964:Leukocytosis / Q000139:chemically induced*; D010446:Peptide Fragments / Q000032:analysis / Q000138:chemical synthesis; D011487:Protein Conformation; D011817:Rabbits; D012882:Skin Tests; D013997:Time Factors
D000706:Anaphylatoxins; D003176:Complement C3; D003182:Complement C5; D010446:Peptide Fragments; C044383:complement C3d-k; D015926:Complement C3a; D003179:Complement C3b; D015933:Complement C3d; D015936:Complement C5a