Cg. Llewellynjones et al., POTENTIAL ROLE OF RECOMBINANT SECRETORY LEUCOPROTEASE INHIBITOR IN THE PREVENTION OF NEUTROPHIL-MEDIATED MATRIX DEGRADATION, Thorax, 49(6), 1994, pp. 567-572
Background - Neutrophil elastase is able to degrade connective tissue
matrices and is thought to be involved in the pathogenesis of destruct
ive lung diseases. Methods - The ability of recombinant secretory leuc
oprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation
of fibronectin in vitro is demonstrated and its efficacy compared wit
h native alpha-1-proteinase inhibitor (n alpha(1)-PI), recombinant alp
ha-1-proteinase inhibitor (r alpha(1)-PI), and the chemical elastase i
nhibitor ICI 200 355. Results - When preincubated with neutrophils bot
h rSLPI and r alpha(1)-PI were effective inhibitors of fibronectin deg
radation although n alpha(1)-PI and ICI 200 355 were less effective. R
ecombinant SLPI was the most effective inhibitor when the cells were a
llowed to adhere to fibronectin before the addition of the inhibitors.
Preincubation of rSLPI (0.1 mu mol/l) with the fibronectin plate resu
lted in almost total inhibition of fibronectin degradation (reduced to
3.3 (SE 0.9)% of control), Pretreating the fibronectin plate with 1 m
u mol/l rSLPI, r alpha(1)-PI and ICI 200 355 followed by thorough wash
ing before the addition of cells resulted in no inhibition of fibronec
tin degradation with r alpha(1)-PI and the ICI inhibitor, but rSLPI re
tained its inhibitory effect. This effect could be reduced by adding r
SLPI in high pH buffer or 2 mol/l NaCl. Conclusions - It is postulated
that rSLPI binds to fibronectin to form a protective layer which prev
ents its degradation by neutrophil elastase. It may prove to be the mo
st useful therapeutic agent in the prevention of neutrophil mediated l
ung damage.