Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.
BACKGROUND
Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases.


METHODS
The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355.


RESULTS
When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl.


CONCLUSIONS
It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.
Llewellyn-Jones
C G
CG
Lung Immunobiochemical Research Laboratory, General Hospital, Birmingham.
Lomas
D A
DA
Stockley
R A
RA
D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000378:metabolism*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D005353:Fibronectins; D009842:Oligopeptides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011994:Recombinant Proteins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; C069366:ICI 200355; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase