PMID- 30021208 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 177 IP - 3 DP - 2018 TI - Degradation of Monocyte Chemoattractant Protein-1 by Tryptase Co-Released in Immunoglobulin E-Dependent Activation of Primary Human Cultured Mast Cells. PG - 199-206 LID - 10.1159/000490533 [doi] AB - BACKGROUND: Mast cells are key immune effector cells which release chemokines, proteases, and other inflammatory mediators upon activation by immunological stimuli. The aim of this study was to investigate the effects of co-releasing proteases on the kinetics of release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in immunoglobulin E (IgE)-mediated activation of human mast cells. METHODS: Homogenous populations of mature and functional primary human mast cells were generated from CD34+ progenitors originated from buffy coats of healthy adult donors. The releases of MCP-1 from human mast cells in basal conditions and in response to FcepsilonRI cross-linking were assessed at different time points. The effects of different types of protease inhibitors on MCP-1 release from these mast cells under stimulated or unstimulated conditions were also investigated. RESULTS: Cultured human mast cells released MCP-1 in basal conditions and its levels increased in a time-dependent manner. When stimulated by FcepsilonRI cross-linking, the levels of MCP-1 detected in the medium gradually decreased over time after the initial peak induction. Such a decline in MCP-1 levels after IgE-dependent activation was completely prevented by pretreatment with a cocktail of protease inhibitors or the specific tryptase inhibitor APC366. CONCLUSIONS: Direct regulation of MCP-1 expression by co-release of tryptase in cultured human mast cells upon IgE-dependent activation demonstrates a role of the serglycin:serine protease axis in modulation of inflammatory reactions through proteolytic degradation of mediators such as chemokines. CI - (c) 2018 S. Karger AG, Basel. FAU - Tam, Issan Yee San AU - Tam IYS AD - School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, China. FAU - Ng, Chun Wai AU - Ng CW AD - School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, China. FAU - Lau, Hang Yung Alaster AU - Lau HYA AD - School of Biomedical Sciences, Faculty of Medicine, Chinese University of Hong Kong, Shatin, China. FAU - Tam, See-Ying AU - Tam SY AD - Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. AD - Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California, USA. LA - eng PT - Journal Article DEP - 20180718 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Protease Inhibitors) RN - 0 (Proteoglycans) RN - 0 (Receptors, IgE) RN - 0 (Vesicular Transport Proteins) RN - 0 (serglycin) RN - 37341-29-0 (Immunoglobulin E) RN - EC 3.4.- (Serine Proteases) RN - EC 3.4.21.59 (Tryptases) SB - IM MH - Cell Degranulation/immunology MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Histamine Release/immunology MH - Humans MH - Immunoglobulin E/*immunology MH - Mast Cells/*immunology/physiology MH - Protease Inhibitors/pharmacology MH - Proteoglycans/*metabolism MH - Receptors, IgE/immunology/metabolism MH - Serine Proteases/*metabolism MH - Tryptases/antagonists & inhibitors/*metabolism MH - Vesicular Transport Proteins/*metabolism OTO - NOTNLM OT - Human mast cells OT - Immunoglobulin E OT - Mast cell tryptase OT - Mediator release OT - Monocyte chemoattractant protein-1 EDAT- 2018/07/19 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/07/19 06:00 PHST- 2018/04/12 00:00 [received] PHST- 2018/05/29 00:00 [accepted] PHST- 2018/07/19 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/07/19 06:00 [entrez] AID - 000490533 [pii] AID - 10.1159/000490533 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2018;177(3):199-206. doi: 10.1159/000490533. Epub 2018 Jul 18.