title: Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils.
abstract: Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation. It has been shown to be synthesized and secreted in vitro by epithelial cells and has been localized in tracheal glands and bronchiolar epithelial cells by immunocytochemistry. In this study, using immunodetection and immunopurification techniques with specific anti-SLPI immunoglobulin G (IgG), we show that SLPI is present as a native 14-kDa molecule in neutrophil cytosol. In addition, we demonstrate that SLPI is the major inhibitor of HLE present in neutrophil cytosol because pre-incubation with specific anti-SLPI IgG was able to inhibit completely the anti-HLE activity of the cytosol. SLPI can be secreted (probably in an inactive form) by neutrophils and its secretion is enhanced when the cells are stimulated with phorbol myristate acetate (PMA). Elafin, an elastase-specific inhibitor, is also present in minute amounts in neutrophil cytosol and its secretion can be up-regulated. The presence of SLPI in the cytosol of neutrophils may serve as a protective screen against proteinases spilling from azurophilic granules. An alternative or supplementary role may be the maintenance of a differentiated phenotype.
authors.affiliation: Department of Pathology, St. Joseph Hospital, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Sallenave
authors.forename: M
authors.initials: M
authors.lastname: Si Tahar
authors.forename: G
authors.initials: G
authors.lastname: Cox
authors.forename: M
authors.initials: M
authors.lastname: Chignard
authors.forename: J
authors.initials: J
authors.lastname: Gauldie
mesh_terms: D002454:Cell Differentiation; D003593:Cytoplasm / Q000737:chemistry / Q000201:enzymology; D018922:HL-60 Cells; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000097:blood; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D013183:Sputum / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate