title: Local regulation of neutrophil elastase activity by endogenous α1-antitrypsin in lipopolysaccharide-primed hematological cells.
abstract: Neutrophil elastase released from activated neutrophils contributes in combating bacterial infection. While chronic inflammation results in anemia and decreased bone marrow activities, little is known about the effect of neutrophil elastase on hematological cell growth in severe inflammatory states. Here, we demonstrated that α1-antitrypsin, a physiological inhibitor of neutrophil elastase, functions as a regulator for cell growth by neutralizing neutrophil elastase activity in lipopolysaccharide-primed hematological cells. HL-60 cells were resistant to neutrophil elastase, as they also expressed α1-antitrypsin. The growth of HL-60 cells transduced with a LentiLox-short hairpin α1-antitrypsin vector was significantly suppressed by neutrophil elastase or lipopolysaccharide. When CD34(+) progenitor cells were differentiated towards a granulocytic lineage, they concomitantly expressed neutrophil elastase and α1-antitrypsin and prevented neutrophil elastase-induced growth inhibition. These results suggest that granulocytes might protect themselves from neutrophil elastase-induced cellular damage by efficiently neutralizing its activity through the simultaneous secretion of endogenous α1-antitrypsin.
authors.affiliation: Research Division of Cell and Molecular Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Dokai
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yasumoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiwata
authors.forename: Asuka
authors.initials: A
authors.lastname: Sakata
authors.forename: Nobuko
authors.initials: N
authors.lastname: Makino
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D048708:Cell Growth Processes / Q000502:physiology; D018922:HL-60 Cells; D006413:Hematopoietic System / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D020014:K562 Cells; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase