Inhibition by recombinant SLPI and half-SLPI (Asn55-Ala107) of elastase and cathepsin G activities: consequence for neutrophil-platelet cooperation

Br J Pharmacol. 1993 Apr;108(4):1100-6. doi: 10.1111/j.1476-5381.1993.tb13511.x.


1. The capacity of recombinant human secretory leukocyte proteinase inhibitor (SLPI) to inhibit human leukocyte elastase (HLE) and cathepsin G (Cat G) was investigated and compared with a recombinant truncated form (carboxyl-terminal domain, Asn55-Ala107) called 1/2 SLPI. 2. Both compounds were efficient when tested against enzymatic activities of purified HLE and Cat G indicating that the HLE- and Cat G-inhibitory sites were preserved in the truncated form. SLPI and 1/2 SLPI also affected platelet activation induced by 0.2 microM Cat G (IC50 = 112 +/- 13 nM for SLPI and 280 +/- 12 nM for 1/2 SLPI). 3. The effects of SLPI and 1/2 SLPI were then tested against polymorphonuclear neutrophil (PMN)-mediated platelet activation, a cell-to-cell interaction mediated by HLE and Cat G released from PMN. In this experimental system, addition of SLPI or 1/2 SLPI before N-formyl-Met-Leu-Phe (fMLP) led to the inhibition of the resulting platelet activation. As was the case for Cat G enzymatic activity and Cat G-induced platelet activation, SLPI was more efficient than 1/2 SLPI (IC50 = 676 +/- 69 nM vs 1121 +/- 150 nM). 4. The ratio of the IC50 against PMN-mediated platelet activation compared to purified Cat G-mediated platelet activation was 6.03 for SLPI and 4.32 for 1/2 SLPI. This difference may be due to the smaller size of the truncated form which could allow this molecule to diffuse more easily between PMN and platelets. 5. In conclusion, 1/2 SLPI could be a promising candidate in the treatment of pathological states linked to inflammation in which participation of HLE and Cat G has been evoked.

MeSH terms

  • Amino Acid Sequence
  • Blood Platelets / drug effects*
  • Cathepsin G
  • Cathepsins / antagonists & inhibitors*
  • Glucuronidase / metabolism
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects*
  • Pancreatic Elastase / antagonists & inhibitors*
  • Platelet Aggregation / drug effects
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins*
  • Recombinant Proteins / pharmacology
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Endopeptidases
  • Serine Proteinase Inhibitors / pharmacology*
  • Serotonin / blood


  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • Recombinant Proteins
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors
  • Serotonin
  • N-Formylmethionine Leucyl-Phenylalanine
  • Glucuronidase
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Pancreatic Elastase