Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III

Cytokine. 1991 Jul;3(4):311-21. doi: 10.1016/1043-4666(91)90499-4.

Abstract

We have investigated the conditions that lead to the generation of the neutrophil-activating peptide 2 (NAP-2) from its precursor, the platelet-derived connective tissue-activating peptide III (CTAP-III). Lysed platelets were found to contain predominantly CTAP-III in the cytosolic fraction, but further truncated derivatives, among these NAP-2, occurred tightly bound to the membrane fraction of fresh platelets. NAP-2 biological activity, as measured by the induction of enzyme release in human neutrophils [polymorphonuclear leukocytes (PMN)] was released by stimulated platelets to a low degree. Much higher activities were formed in the presence of peripheral blood leukocytes. Coincubation of CTAP-III with PMN resulted in the almost complete conversion of the precursor to NAP-2, as did incubation of CTAP-III with PMN-conditioned medium. In both situations, the generation of NAP-2 could be prevented by serine-protease inhibitor phenylmethylsulfonyl fluoride but not by inhibitors specific for Ca(2+)-dependent or thiol proteases. From several PMN-derived proteases tested, only cathepsin G had the capacity to cleave CTAP-III into NAP-2 with high specificity and in a relatively short period of time (30 min). Our data indicate that NAP-2, released by platelets in small quantities, could cause PMN to enter into a positive feedback cycle by initiating the secretion of serine proteases, which in turn could convert platelet-derived CTAP-III into biologically active NAP-2.

MeSH terms

  • Amino Acid Sequence
  • Blood Coagulation Factors / chemistry
  • Blood Coagulation Factors / metabolism
  • Blood Platelets / immunology
  • Blood Platelets / metabolism
  • Humans
  • In Vitro Techniques
  • Interleukin-8 / biosynthesis*
  • Molecular Sequence Data
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Peptides*
  • Serine Endopeptidases / metabolism
  • Subcellular Fractions / immunology
  • Subcellular Fractions / metabolism

Substances

  • Blood Coagulation Factors
  • Interleukin-8
  • Peptides
  • connective tissue-activating peptide
  • low affinity platelet factor 4
  • Serine Endopeptidases