PMID- 9987080
OWN - NLM
STAT- MEDLINE
DCOM- 19990415
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 55
IP  - 2
DP  - 1999 Feb
TI  - Extracellular matrix regulates apoptosis in human neutrophils.
PG  - 562-71
AB  - BACKGROUND: During inflammation, polymorphonuclear neutrophils (PMNs) migrate 
      into the affected tissue interacting with extracellular matrix (ECM) proteins. We 
      tested the hypothesis that PMN-matrix interaction affects PMN apoptosis. METHODS: 
      Apoptosis of human PMNs was detected by DNA-fragmentation assay and was 
      quantitated by flow cytometry, ultraviolet and light microscopy. Cell adhesion 
      was assessed by a toluidine blue assay, and cell spreading was detected by phase 
      contrast microscopy. Protein tyrosine phosphorylation was studied using Western 
      blotting and confocal microscopy. RESULTS: PMN apoptosis was not different in 
      unstimulated cultures on either surface-adherent fibronectin or on PolyHema, a 
      surface that prevents cell adherence. However, tumor necrosis factor-alpha (TNF 
      alpha) treatment significantly increased apoptosis on fibronectin (37 +/- 4%) 
      compared with PolyHema (20 +/- 3%). Tests on other matrix substances revealed 
      that the percentage of apoptotic PMNs in the presence of TNF alpha was 8 +/- 1% 
      on PolyHema, 26 +/- 4% on fibronectin, 17 +/- 2% on collagen I, 16 +/- 2% on 
      collagen IV, and 16 +/- 3% on laminin (P < 0.05 for all matrices compared with 
      PolyHema). Preincubation with genistein (50 microM) significantly inhibited TNF 
      alpha-mediated apoptosis on fibronectin (39 +/- 4% to 21 +/- 4%) but not on 
      PolyHema (21 +/- 4% to 16 +/- 4%). Genistein also reduced PMN spreading on 
      fibronectin. In contrast, inhibitors of mitogen-activated protein kinase and 
      protein kinase C showed no effect on PMN apoptosis. Fibronectin strongly 
      increased tyrosine phosphorylation of three 102, 63, and 54 kDa proteins. Five 
      newly tyrosine-phosphorylated 185, 85, 66, 56, and 42 kDa bands were also 
      visible. Using confocal microscopy, highest tyrosine phosphorylation was 
      localized to sites of cell-matrix interaction. CONCLUSIONS: ECM influences 
      apoptosis in TNF alpha-activated, adherent, spreading PMNs. The process is 
      regulated by tyrosine phosphorylation. Acceleration of apoptosis may shorten the 
      PMN lifespan and thereby locally regulate inflammation.
FAU - Kettritz, R
AU  - Kettritz R
AD  - Franz-Volhard Clinic, Germany.
FAU - Xu, Y X
AU  - Xu YX
FAU - Kerren, T
AU  - Kerren T
FAU - Quass, P
AU  - Quass P
FAU - Klein, J B
AU  - Klein JB
FAU - Luft, F C
AU  - Luft FC
FAU - Haller, H
AU  - Haller H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Fibronectins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 25249-16-5 (Polyhydroxyethyl Methacrylate)
RN  - 42HK56048U (Tyrosine)
RN  - DH2M523P0H (Genistein)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Cell Adhesion/drug effects
MH  - Extracellular Matrix/*physiology
MH  - Fibronectins/physiology
MH  - Genistein/pharmacology
MH  - Humans
MH  - Neutrophils/drug effects/*physiology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Polyhydroxyethyl Methacrylate
MH  - Time Factors
MH  - Tissue Distribution/physiology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Tyrosine/metabolism
EDAT- 1999/02/13 00:00
MHDA- 1999/02/13 00:01
CRDT- 1999/02/13 00:00
PHST- 1999/02/13 00:00 [pubmed]
PHST- 1999/02/13 00:01 [medline]
PHST- 1999/02/13 00:00 [entrez]
AID - S0085-2538(15)46000-4 [pii]
AID - 10.1046/j.1523-1755.1999.00280.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Feb;55(2):562-71. doi: 10.1046/j.1523-1755.1999.00280.x.