PMID- 10512690
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20131121
IS  - 1096-6374 (Print)
IS  - 1096-6374 (Linking)
VI  - 9
IP  - 4
DP  - 1999 Aug
TI  - Inflammation-related neutrophil proteases, cathepsin G and elastase, function as 
      insulin-like growth factor binding protein proteases.
PG  - 241-53
AB  - Over the past few years, several proteolytic enzymes have been identified as
      insulin-like growth factor binding protein (IGFBP) proteases. It has been
      suggested that proteolytic cleavage of IGFBPs is associated with regulation of
      the proliferative effects of IGFs on their target cells. In this study, we have
      demonstrated that two neutrophil proteases, cathepsin G and elastase, effectively
      cleave IGFBPs in vitro and in vivo at concentrations lower than previous
      described IGFBP proteases. Purified leukocyte cathepsin G and elastase cleaved
      all six well-characterized IGFBPs into distinct fragments in a
      concentration-dependent manner. Under similar experimental conditions, cathepsin 
      G preferentially cleaved IGFBP-5, followed by BP-2, BP-3, BP-4, BP-1, and BP-6.
      In comparison, elastase equally preferred IGFBP-3 and IGFBP-4, followed by BP-1, 
      BP-5, BP-6, and BP-2. Proteolysis of rh(125)I-IGFBP-3 by cathepsin G was blocked 
      by alpha(1)-antichymotrypsin, while elastase proteolytic activity was blocked by 
      alpha(1)-proteinase inhibitor as expected. Elastase, but not cathepsin G, cleaved
      free IGF-I into a smaller molecular weight fragment in vitro, possibly
      designating unique functions for each protease within the IGF axis. Sequence
      analysis of IGFBP-3 fragments produced by cathepsin G and elastase demonstrated
      that each protease cleaved IGFBP-3 at unique sites within its midregion. More
      importantly, extracts from purified neutrophils have demonstrated significant
      proteolytic cleavage of IGFBP-3 that resembles elastase proteolysis of IGFBP-3.
      Recent studies using a monocyte-like cell model have also shown significant
      cleavage of IGFBP-3. These in vitro and in vivo data suggest that the neutrophil 
      proteases, cathepsin G and elastase, in addition to their previously described
      functions as extracellular matrix-degrading enzymes, may potentially act as IGFBP
      proteases involved in regulation of IGFs and IGFBPs during inflammation and wound
      healing.
CI  - Copyright 1999 Harcourt Publishers Ltd.
FAU - Gibson, T L
AU  - Gibson TL
AD  - Department of Biochemistry and Biophysics, University of Pennsylvania,
      Philadelphia, PA, 19104, USA.
FAU - Cohen, P
AU  - Cohen P
LA  - eng
GR  - 1P01 HL56398/HL/NHLBI NIH HHS/United States
GR  - 2R01 DK47591/DK/NIDDK NIH HHS/United States
GR  - R01 AI40203/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Scotland
TA  - Growth Horm IGF Res
JT  - Growth hormone & IGF research : official journal of the Growth Hormone Research
      Society and the International IGF Research Society
JID - 9814320
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 1)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 2)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 3)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 5)
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Trypsin Inhibitor, Bowman-Birk Soybean)
RN  - 0 (alpha 1-Antichymotrypsin)
RN  - 57KD15003I (Phenylmethylsulfonyl Fluoride)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.20 (CTSG protein, human)
RN  - EC 3.4.21.20 (Cathepsin G)
RN  - EC 3.4.21.36 (Pancreatic Elastase)
SB  - IM
MH  - Cathepsin G
MH  - Cathepsins/antagonists & inhibitors/*metabolism
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Humans
MH  - Immunoblotting
MH  - Inflammation/*metabolism
MH  - Insulin-Like Growth Factor Binding Protein 1/metabolism
MH  - Insulin-Like Growth Factor Binding Protein 2/metabolism
MH  - Insulin-Like Growth Factor Binding Protein 3/metabolism
MH  - Insulin-Like Growth Factor Binding Protein 5/metabolism
MH  - Insulin-Like Growth Factor Binding Proteins/*metabolism
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Neutrophils/*metabolism
MH  - Pancreatic Elastase/antagonists & inhibitors/*metabolism
MH  - Peptide Fragments/analysis/metabolism
MH  - Phenylmethylsulfonyl Fluoride/pharmacology
MH  - Protease Inhibitors/pharmacology
MH  - Sequence Analysis, Protein
MH  - Serine Endopeptidases
MH  - Trypsin Inhibitor, Bowman-Birk Soybean/pharmacology
MH  - alpha 1-Antichymotrypsin/pharmacology
EDAT- 1999/10/08 00:00
MHDA- 1999/10/08 00:01
CRDT- 1999/10/08 00:00
PHST- 1999/10/08 00:00 [pubmed]
PHST- 1999/10/08 00:01 [medline]
PHST- 1999/10/08 00:00 [entrez]
AID - 10.1054/ghir.1999.0115 [doi]
AID - S1096-6374(99)90115-6 [pii]
PST - ppublish
SO  - Growth Horm IGF Res. 1999 Aug;9(4):241-53. doi: 10.1054/ghir.1999.0115.