title: Human mast cells produce and release the cytotoxic lymphocyte associated protease granzyme B upon activation.
abstract: Mast cells are widely distributed throughout the body and express effector functions in allergic reactions, inflammatory diseases, and host defense. Activation of mast cells results in exocytosis of preformed chemical mediators and leads to novel synthesis and secretion of lipid mediators and cytokines. Here, we show that human mast cells also express and release the cytotoxic lymphocyte-associated protease, granzyme B. Granzyme B was active and localized in cytoplasmic granules, morphologically resembling those present in cytotoxic lymphocytes. Expression and release of granzyme B by mast cell-lines HMC-1 and LAD 2 and by cord blood- and mature skin-derived human mast cells depended on the mode of activation of these cells. In mast cell lines and cord blood-derived mast cells, granzyme B expression was mainly induced by non-physiological stimuli (A23187/PMA, Compound 48/80) and substance P. In contrast, mature skin-derived mast cells only produced granzyme B upon IgE-dependent stimulation. We conclude that granzyme B is expressed and released by human mast cells upon physiologic stimulation. This suggests a role for granzyme B as a novel mediator in mast cell biology.
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Merel C M
authors.initials: MC
authors.lastname: Strik
authors.forename: Pieter J A
authors.initials: PJ
authors.lastname: de Koning
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Kleijmeer
authors.forename: Bellinda A
authors.initials: BA
authors.lastname: Bladergroen
authors.forename: Angela M
authors.initials: AM
authors.lastname: Wolbink
authors.forename: Janice M
authors.initials: JM
authors.lastname: Griffith
authors.forename: Dorine
authors.initials: D
authors.lastname: Wouters
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukuoka
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: S Marieke
authors.initials: SM
authors.lastname: van Ham
authors.forename: J Alain
authors.initials: JA
authors.lastname: Kummer
mesh_terms: D000328:Adult; D000941:Antigens / Q000276:immunology; D002478:Cells, Cultured; D004790:Enzyme Induction; D005260:Female; D005786:Gene Expression Regulation; D053804:Granzymes / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism* / Q000648:ultrastructure; D008415:Mastocytosis / Q000201:enzymology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D015843:Serpins / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism
chemical_list: D000941:Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; C102316:SERPINB9 protein, human; D015843:Serpins; D054353:Perforin; D053804:Granzymes; D053802:Tryptases