PMID- 15161642
OWN - NLM
STAT- MEDLINE
DCOM- 20040708
LR  - 20190607
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 164
IP  - 6
DP  - 2004 Jun
TI  - Role of leukocyte elastase in preventing cellular re-colonization of the mural 
      thrombus.
PG  - 2077-87
AB  - To explore possible mechanisms responsible for the absence of cell 
      re-colonization of mural thrombi in aneurysms, we analyzed the release and 
      storage of leukocyte proteases in the most luminal layer versus intermediate and 
      abluminal layers of 10 mural thrombi of human abdominal aortic aneurysms. The 
      luminal layer contained many polymorphonuclear leukocytes (PMNs), which released 
      pro-matrix metalloproteinase (MMP)-9 and MMP-8. Leukocyte elastase was also 
      stored and released by the luminal layer (immunohistochemistry, activity on 
      synthetic substrates, and casein zymography). Acid buffer allowed extraction of 
      leukocyte elastase from the luminal layer, which was inhibited by elastase 
      inhibitors. Casein zymography of luminal extracts and conditioned medium from 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMNs exhibited a similar 
      lysis pattern, corresponding to elastase activity. Smooth muscle cell (SMC) 
      seeding resulted in colonization of the intermediate thrombus layer ex vivo but 
      not of the luminal layer. Extracts of the luminal layer induced loss of anchorage 
      of both cultured human smooth muscle cells and stromal cells of bone marrow 
      origin (anoikis). This anoikis was prevented by preincubation of the extracts 
      with serine protease inhibitors. Moreover, adhesion of human SMCs and stromal 
      bone marrow cells on fibrin gels was strongly inhibited when the gel was 
      preincubated with pure elastase, medium of fMLP-stimulated PMNs, or extracts of 
      luminal layers of mural thrombi. This loss of cell anchorage was prevented by the 
      preincubation of the medium or extracts with alpha(1)-antitrypsin, but not when 
      alpha(1)-antitrypsin was added after binding of elastase to the fibrin gel. In 
      conclusion, elastase released by PMNs trapped within the mural thrombus impairs 
      the spontaneous anchorage of mesenchymal cells to a fibrin matrix. This 
      phenomenon could be one mechanism by which cellular healing of the mural thrombus 
      in aneurysms is prevented.
FAU - Fontaine, Vincent
AU  - Fontaine V
AD  - Institut National de la Sante et de la Recherche Medicale (INSERM) Unit 460, 
      Cardiovascular Remodeling, Centre Hospitale Universitaire (CHU) Xavier Bichat, 
      Paris, France.
FAU - Touat, Ziad
AU  - Touat Z
FAU - Mtairag, El Mostafa
AU  - Mtairag el M
FAU - Vranckx, Roger
AU  - Vranckx R
FAU - Louedec, Liliane
AU  - Louedec L
FAU - Houard, Xavier
AU  - Houard X
FAU - Andreassian, Bernard
AU  - Andreassian B
FAU - Sebbag, Uriel
AU  - Sebbag U
FAU - Palombi, Tonino
AU  - Palombi T
FAU - Jacob, Marie-Paule
AU  - Jacob MP
FAU - Meilhac, Olivier
AU  - Meilhac O
FAU - Michel, Jean-Baptiste
AU  - Michel JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Fibronectins)
RN  - 0 (Serine Proteinase Inhibitors)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Aneurysm/enzymology/pathology/surgery
MH  - Anoikis/drug effects
MH  - Bone Marrow Cells/cytology
MH  - Cell Adhesion
MH  - Cell Culture Techniques
MH  - Fibronectins/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Leukocyte Elastase/*physiology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Muscle, Smooth, Vascular/cytology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/enzymology/pathology/physiology
MH  - Serine Proteinase Inhibitors/pharmacology
MH  - Stromal Cells/cytology/physiology
MH  - Thrombosis/*enzymology/pathology
PMC - PMC1615778
EDAT- 2004/05/27 05:00
MHDA- 2004/07/09 05:00
PMCR- 2004/12/01
CRDT- 2004/05/27 05:00
PHST- 2004/05/27 05:00 [pubmed]
PHST- 2004/07/09 05:00 [medline]
PHST- 2004/05/27 05:00 [entrez]
PHST- 2004/12/01 00:00 [pmc-release]
AID - S0002-9440(10)63766-2 [pii]
AID - 10.1016/s0002-9440(10)63766-2 [doi]
PST - ppublish
SO  - Am J Pathol. 2004 Jun;164(6):2077-87. doi: 10.1016/s0002-9440(10)63766-2.