Release of neutrophil proteinase 4(3) and leukocyte elastase during phagocytosis and their interaction with proteinase inhibitors.
Neutrophil proteinase 4 (NP4) is a major neutral proteinase of the human polymorphonuclear (PMN) leukocyte, which is present in amounts similar to leukocyte elastase. NP4(3) is a potent, non-specific proteinase, which may degrade structural and soluble proteins in the tissues and body fluids, and it has been implicated as an important pathogenetic factor in lung emphysema. We have studied the release of elastase and NP4(3) in an in vitro model of phagocytosis. alpha 1-proteinase inhibitor (alpha 1-PI) is the major plasma inhibitor of both leukocyte elastase and NP4(3), but alpha 1-PI bound leukocyte elastase more readily than NP4(3). The basic conditions were designed so that some proteolytic activity was present in the medium. Addition of increasing amounts of Secretory leukocyte protease inhibitor (SLPI) to the incubation mixtures resulted in binding of leukocyte elastase to this inhibitor and extinction of free proteolytic activity against both natural and synthetic substrates. The progressive binding of leukocyte elastase to SLPI instead of alpha 1-PI was paralleled by an increasing binding of NP4(3) to alpha 1-PI. SLPI is a potent inhibitor of leukocyte elastase and cathepsin G, and although it lacks inhibitory effect on NP4(3), it may obviously indirectly aid in the binding and inhibition of NP4(3) to alpha 1-PI, by taking care of at least part of the leukocyte elastase. As a specific NP4(3)-inhibitor is not readily available for therapeutic use, this effect may prove useful under in vivo conditions and enhance the protective effect of administered recombinant human SLPI.
Department of Surgery, Lund University, Malmö General Hospital, Sweden.
M
M
Bergenfeldt
L
L
Axelsson
K
K
Ohlsson
D000595:Amino Acid Sequence; D001710:Biotin; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007120:Immunochemistry; D066298:In Vitro Techniques; D019272:Leukocyte Elastase; D007962:Leukocytes; D008969:Molecular Sequence Data; D053146:Myeloblastin; D010196:Pancreatic Elastase / Q000097:blood*; D010587:Phagocytosis / Q000187:drug effects* / Q000502:physiology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D012697:Serine Endopeptidases / Q000097:blood*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D001710:Biotin; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D053146:Myeloblastin