PMID- 10461681 OWN - NLM STAT- MEDLINE DCOM- 19990930 LR - 20031114 IS - 1078-0297 (Print) IS - 1078-0297 (Linking) VI - 103 IP - 2 DP - 1999 Feb TI - Neutrophil elastase enhances macrophage production of chemokines in receptor-mediated reaction. PG - 139-47 AB - Proteases influence various leukocyte effector functions. We investigated the specific binding activity of neutrophil elastase (NE) on rat peritoneal macrophages to stimulate chemokine production in vitro. NE enhanced macrophage production of monocyte chemo-attractant protein-1 (MCP-1) (CC-chemokine) and cytokine-induced neutrophil chemo-attractant (CINC) (CXC-chemokine). However, the serine protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), significantly reduced these chemokine productions by macrophages stimulated with NE. 125I-NE was significantly bound to macrophages, but 125I-NE binding was inhibited by addition of unlabeled NE. In addition, NE significantly stimulated [3H]thymidine incorporation into DNA on 3T3 fibroblasts in a dose-dependent manner. These results suggest that NE stimulates chemokine production by macrophages. This may be a receptor-mediated reaction. Thus, NE not only degrades extra-cellular matrix but also stimulates chemokine production by macrophages. FAU - Ishihara, K AU - Ishihara K AD - Department of Surgery II, Kumamoto University Medical School, Japan. FAU - Yamaguchi, Y AU - Yamaguchi Y FAU - Okabe, K AU - Okabe K FAU - Ogawa, M AU - Ogawa M LA - eng PT - Journal Article PL - United States TA - Res Commun Mol Pathol Pharmacol JT - Research communications in molecular pathology and pharmacology JID - 9437512 RN - 0 (Chemokines) RN - 0 (Receptors, Cell Surface) RN - EC 3.4.21.37 (Leukocyte Elastase) SB - IM MH - 3T3 Cells MH - Animals MH - Chemokines/*biosynthesis MH - Leukocyte Elastase/*metabolism MH - Macrophages, Peritoneal/*metabolism MH - Male MH - Mice MH - Rats MH - Rats, Wistar MH - Receptors, Cell Surface/*metabolism EDAT- 1999/08/26 00:00 MHDA- 1999/08/26 00:01 CRDT- 1999/08/26 00:00 PHST- 1999/08/26 00:00 [pubmed] PHST- 1999/08/26 00:01 [medline] PHST- 1999/08/26 00:00 [entrez] PST - ppublish SO - Res Commun Mol Pathol Pharmacol. 1999 Feb;103(2):139-47.