June 1988 | KOUJI MATSUSHIMA, KAZUHIRO MORISHITA, TEIZO YOSHIMURA, SUKADEV LAVU, YOSHIRO KOBAYASHI, WOOK LEW, ETTORE APPELLA, HSIANG F. KUNG, EDWARD J. LEONARD, JOOST J. OPPENHEIM
The study reports the molecular cloning and sequencing of the full-length cDNA for a human monocyte-derived neutrophil chemotactic factor (MDNCF). The cDNA encodes a 99-amino acid polypeptide with a putative signal sequence, and the mature protein consists of 72 amino acids starting with serine at residue 28. The deduced amino acid sequence of MDNCF shows striking similarity to several platelet-derived factors, a v-src-induced protein, a growth-regulated gene product, and an IFN-γ inducible protein. The cDNA was used as a probe to identify inducers of MDNCF mRNA expression in human peripheral blood mononuclear cells (PBMC). MDNCF mRNA was increased >10-fold within 1 hour after stimulation with LPS, IL-1, or TNF, but not by IFN-γ, IFN-α, or IL-2. LPS, IL-1, and TNF stimulated mononuclear cells to produce biologically active MDNCF. This observation may account for the in vivo capacity of IL-1 and TNF to induce neutrophil infiltrates. The study also shows that IL-1 and TNF induce MDNCF production, which may contribute to the inflammatory response by inducing both adhesive and chemotactic molecules. The cloning of MDNCF provides the basis for recombinant and chemical synthesis of the molecule, enabling further studies on its sites of synthesis, receptors, and role in acute and chronic inflammation.The study reports the molecular cloning and sequencing of the full-length cDNA for a human monocyte-derived neutrophil chemotactic factor (MDNCF). The cDNA encodes a 99-amino acid polypeptide with a putative signal sequence, and the mature protein consists of 72 amino acids starting with serine at residue 28. The deduced amino acid sequence of MDNCF shows striking similarity to several platelet-derived factors, a v-src-induced protein, a growth-regulated gene product, and an IFN-γ inducible protein. The cDNA was used as a probe to identify inducers of MDNCF mRNA expression in human peripheral blood mononuclear cells (PBMC). MDNCF mRNA was increased >10-fold within 1 hour after stimulation with LPS, IL-1, or TNF, but not by IFN-γ, IFN-α, or IL-2. LPS, IL-1, and TNF stimulated mononuclear cells to produce biologically active MDNCF. This observation may account for the in vivo capacity of IL-1 and TNF to induce neutrophil infiltrates. The study also shows that IL-1 and TNF induce MDNCF production, which may contribute to the inflammatory response by inducing both adhesive and chemotactic molecules. The cloning of MDNCF provides the basis for recombinant and chemical synthesis of the molecule, enabling further studies on its sites of synthesis, receptors, and role in acute and chronic inflammation.
[slides] Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor | StudySpace