PMID- 11368345
OWN - NLM
STAT- MEDLINE
DCOM- 20010607
LR  - 20190629
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 386
IP  - 2
DP  - 2001 Feb 15
TI  - Effects of noninhibitory alpha-1-antitrypsin on primary human monocyte activation 
      in vitro.
PG  - 221-6
AB  - A major function of alpha-1-antitrypsin (AAT) is the inhibition of overexpressed 
      serine proteinases during inflammation. However, it is also known that the 
      biological activity of AAT is affected by chemical modifications, including 
      oxidation of the reactive-site methionine, polymerization, and cleavage by 
      unspecific proteases, all of which will result in AAT inactivation and/or 
      degradation. All inactive forms of AAT can be detected in tissues and fluids 
      recovered from inflammatory sites. To test for a possible link between the 
      inflammation-generated, noninhibitory, cleaved form of AAT and cellular processes 
      associated with inflammation, we studied the effects of this form at varying 
      concentrations on human monocytes in culture. We found that cleaved AAT at 
      concentrations ranging between 1 and 10 microM in monocyte cultures over 24 h 
      induces elevation in monocyte chemoattractant protein-1 (MCP-1) and 
      pro-inflammatory cytokines such as TNFalpha and IL-6 and also increases 
      production of interstitial collagenase (MMP-1) and gelatinase B (MMP-9), members 
      of two different classes of matrix metalloproteinase. Moreover, monocytes 
      stimulated with higher doses of cleaved AAT show an increase in cellular oxygen 
      consumption by about 30%, while native AAT under the same experimental conditions 
      inhibits oxygen consumption by about 50%. These results indicate that the cleaved 
      form of AAT may play a role in monocyte recruitment and pro-inflammatory 
      activation during inflammatory processes, and also suggest that changes in 
      structure occurring upon AAT cleavage could alter its functional properties with 
      potential pathological consequences.
FAU - Moraga, F
AU  - Moraga F
AD  - Department of Medicine, University Hospital Malmo, Sweden.
FAU - Lindgren, S
AU  - Lindgren S
FAU - Janciaskiene, S
AU  - Janciaskiene S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (alpha 1-Antitrypsin)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interleukin-6/metabolism
MH  - Macrophage Activation/*drug effects
MH  - Matrix Metalloproteinase 1/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Monocytes/cytology/*drug effects/enzymology/metabolism
MH  - Oxygen Consumption/drug effects
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - alpha 1-Antitrypsin/metabolism/*pharmacology
EDAT- 2001/05/23 10:00
MHDA- 2001/06/08 10:01
CRDT- 2001/05/23 10:00
PHST- 2001/05/23 10:00 [pubmed]
PHST- 2001/06/08 10:01 [medline]
PHST- 2001/05/23 10:00 [entrez]
AID - S0003986100922112 [pii]
AID - 10.1006/abbi.2000.2211 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2001 Feb 15;386(2):221-6. doi: 10.1006/abbi.2000.2211.