title: Inactivated pepsin inhibits neutrophil activation by Fcgamma-receptor-dependent and independent stimuli.
abstract: Pepsin is widely used to produce F(ab')2 fragments of immunoglobulin G (IgG). In many cases, at least part of the pepsin will remain present in the F(ab')2 preparation, albeit in (irreversibly) inactivated form. Here we report on a potent immunomodulatory effect of irreversibly inactivated pepsin on activated human neutrophils. Degranulation, induced by coated IgG or via cytochalasin B/N-formyl-Met-Leu-Phe, was measured by quantifying elastase release, and was found to be inhibited in a dose-dependent manner by inactivated pepsin. Since a number of intravenous immunoglobulin (IVIg) products are also treated by limited digestion with pepsin, we investigated if pepsin would be present in quantities large enough to inhibit neutrophil activation. The amounts of pepsin detected in three different pepsin-treated IVIg products were found to be too low to induce an effect, at least in an in vitro setting.
authors.affiliation: Sanquin Research, Department of Immunopathology, Amsterdam, The Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Iwan
authors.initials: I
authors.lastname: Kustiawan
authors.affiliation: Sanquin Research, Department of Immunopathology, Amsterdam, The Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Ninotska
authors.initials: N
authors.lastname: Derksen
authors.affiliation: Sanquin Research, Department of Immunopathology, Amsterdam, The Netherlands; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. Electronic address: T.Rispens@sanquin.nl.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
mesh_terms: D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000378:metabolism / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism / Q000494:pharmacology*; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: C489017:FCGR1A protein, human; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase; D010434:Pepsin A
keywords: Immunomodulation; Intravenous immunoglobulin (IVIg); Neutrophil; Pepsin