Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils

Patrizia Scapini, Lorella Nesi, Monica Morini, Elena Tanghetti, Mirella Belleri, Douglas Noonan, Marco Presta, Adriana Albini, Marco A. Cassatella

Research output: Contribution to journalArticle

Abstract

The contribution of polymorphonuclear neutrophils (PMN) to host defense and natural immunity extends well beyond their traditional role as professional phagocytes. In this study, we demonstrate that upon stimulation with proinflammatory stimuli, human PMN release enzymatic activities that, in vitro, generate bioactive angiostatin fragments from purified plasminogen. We also provide evidence that these angiostatin-like fragments, comprising kringle domain 1 to kringle domain 3 (kringle 1-3) of plasminogen, are generated as a byproduct of the selective proteolytic activity of neutrophil-secreted elastase. Remarkably, affinity-purified angiostatin kringle 1-3 fragments generated by neutrophils inhibited basic fibroblast growth factor plus vascular endothelial growth factor-induced endothelial cell proliferation in vitro, and both vascular endothelial growth factor-induced angiogenesis in the matrigel plug assay and fibroblast growth factor-induced angiogenesis in the chick embryo chorioallantoic membrane assay, in vivo. These results represent the first demonstration that biologically active angiostatin-like fragments can be generated by inflammatory human neutrophils. Because angiostatin is a potent inhibitor of angiogenesis, tumor growth, and metastasis, the data suggest that activated PMN not only act as potent effectors of inflammation, but might also play a critical role in the inhibition of angiogenesis in inflammatory diseases and tumors, by generation of a potent anti-angiogenic molecule.

Original languageEnglish
Pages (from-to)5798-5804
Number of pages7
JournalJournal of Immunology
Volume168
Issue number11
Publication statusPublished - Jun 1 2002

Fingerprint

Angiostatins
Kringles
Neutrophils
Plasminogen
Vascular Endothelial Growth Factor A
Chorioallantoic Membrane
Professional Role
Leukocyte Elastase
Angiogenesis Inhibitors
Fibroblast Growth Factors
Fibroblast Growth Factor 2
Chick Embryo
Phagocytes
Innate Immunity
Neoplasms
Endothelial Cells
Cell Proliferation
Neoplasm Metastasis
Inflammation
Growth

ASJC Scopus subject areas

  • Immunology

Cite this

Scapini, P., Nesi, L., Morini, M., Tanghetti, E., Belleri, M., Noonan, D., ... Cassatella, M. A. (2002). Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. Journal of Immunology, 168(11), 5798-5804.

Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. / Scapini, Patrizia; Nesi, Lorella; Morini, Monica; Tanghetti, Elena; Belleri, Mirella; Noonan, Douglas; Presta, Marco; Albini, Adriana; Cassatella, Marco A.

In: Journal of Immunology, Vol. 168, No. 11, 01.06.2002, p. 5798-5804.

Research output: Contribution to journalArticle

Scapini, P, Nesi, L, Morini, M, Tanghetti, E, Belleri, M, Noonan, D, Presta, M, Albini, A & Cassatella, MA 2002, 'Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils', Journal of Immunology, vol. 168, no. 11, pp. 5798-5804.
Scapini P, Nesi L, Morini M, Tanghetti E, Belleri M, Noonan D et al. Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. Journal of Immunology. 2002 Jun 1;168(11):5798-5804.
Scapini, Patrizia ; Nesi, Lorella ; Morini, Monica ; Tanghetti, Elena ; Belleri, Mirella ; Noonan, Douglas ; Presta, Marco ; Albini, Adriana ; Cassatella, Marco A. / Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. In: Journal of Immunology. 2002 ; Vol. 168, No. 11. pp. 5798-5804.
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