Leukocyte-derived growth factor links the PDGF and CXC chemokine families of peptides.

Abstract

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