LEUKOCYTE-DERIVED GROWTH-FACTOR LINKS THE PDGF AND CXC CHEMOKINE FAMILIES OF PEPTIDES

Leukocytes produce many biological mediators that orchestrate the subs equent cellular events during wound healing, We have identified a nove l cytokine, leukocyte-derived growth factor (LDGF), which is mitogenic for connective tissue cells, Sequence analysis of the LDGF peptide re vealed that it is a precursor of other known peptides including platel et basic protein (PBP), connective tissue activating peptide III (CTAP -III), and neutrophil activating peptide 2 (NAP-2). None of these shor ter peptides are active as mitogens for fibroblasts, LDGF appears to s timulate fibroblast growth by stimulation of tyrosine kinase activity of the PDGF receptors. One of the truncated products of LDGF, NAP-S, i s a potent neutrophil chemoattractant, Peptides larger than NAP-2, suc h as PBP and CTAP-III, are not active as neutrophil chemoattractants, Collectively, these findings demonstrate that the LDGF peptide must re main intact in order to retain its fibroblast mitogenic activity, If t he LDGF peptide is processed to release the carboxyl terminal half to generate NAP-S, a peptide with proinflammatory activity is generated, These results indicate that the multiple peptides produced from the LD GF-PBP gene posses divergent biological activities that could regulate different phases of the repair process.