PMID- 11722648 OWN - NLM STAT- MEDLINE DCOM- 20011214 LR - 20190513 IS - 0019-2805 (Print) IS - 1365-2567 (Electronic) IS - 0019-2805 (Linking) VI - 104 IP - 3 DP - 2001 Nov TI - Rat mast cell protease-I enhances immunoglobulin E production by mouse B cells stimulated with interleukin-4. PG - 333-40 AB - Mast cell chymase plays important roles in inflammation and tissue remodeling. Here we show that mast cell chymase also functions as an enhancer of immunoglobulin production. In the culture of murine spleen cells stimulated with lipopolysaccharide and interleukin-4, purified rat chymase (rat mast cell protease-I; RMCP-I), at physiological concentrations, enhanced immunoglobulin E (IgE) and IgG1 syntheses but not IgG3 synthesis. The enhancement was also evident when spleen cells depleted of T cells and macrophages were employed as responding cells. Enzymatic activity of RMCP-I was required to enhance IgE and IgG1, because two inhibitors for chymotryptic enzymes, chymostatin and Y-40613, a novel chymase inhibitor, suppressed the enhanced immunoglobulin production, and phenylmethylsulphonyl fluoride, an irreversible inhibitor for serine proteases, totally abolished the enhancing effect. Furthermore, a specific inhibitor for Zn2+-dependent metalloproteases, GI 129471, could also completely inhibit the production of IgE and IgG1 that was enhanced by RMCP-I, suggesting that a metalloprotease also played an essential role in the immunoglobulin production. Our results together with others show that proteases from mast cell granules have important function not only in the efferent phase but also in the afferent phase of immune responses. FAU - Yoshikawa, T AU - Yoshikawa T AD - Pharmaceutical Research Division, Mitsubishi Pharma Corporation, Osaka, Japan. FAU - Imada, T AU - Imada T FAU - Nakakubo, H AU - Nakakubo H FAU - Nakamura, N AU - Nakamura N FAU - Naito, K AU - Naito K LA - eng PT - Journal Article PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Immunoglobulin G) RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (Serine Proteinase Inhibitors) RN - 130370-59-1 (GI 129471) RN - 207137-56-2 (Interleukin-4) RN - 37341-29-0 (Immunoglobulin E) RN - 47E5O17Y3R (Phenylalanine) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 3.4.21.39 (Chymases) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Animals MH - B-Lymphocytes/*immunology MH - Cattle MH - Cell Culture Techniques MH - Chymases MH - Dose-Response Relationship, Immunologic MH - Female MH - Immunoglobulin E/*biosynthesis MH - Immunoglobulin G/biosynthesis MH - Interleukin-4/*immunology MH - Lymphocyte Activation/immunology MH - Mast Cells/enzymology/immunology MH - Matrix Metalloproteinase 1 MH - Matrix Metalloproteinase Inhibitors MH - Matrix Metalloproteinases/immunology MH - Mice MH - Mice, Inbred BALB C MH - Phenylalanine/*analogs & derivatives/pharmacology MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Serine Endopeptidases/*immunology MH - Serine Proteinase Inhibitors/pharmacology MH - Spleen/immunology PMC - PMC1783305 EDAT- 2001/11/28 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/11/01 CRDT- 2001/11/28 10:00 PHST- 2001/11/28 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/11/28 10:00 [entrez] PHST- 2002/11/01 00:00 [pmc-release] AID - 1320 [pii] AID - 10.1046/j.1365-2567.2001.01320.x [doi] PST - ppublish SO - Immunology. 2001 Nov;104(3):333-40. doi: 10.1046/j.1365-2567.2001.01320.x.