PMID- 14603221
OWN - NLM
STAT- MEDLINE
DCOM- 20031204
LR  - 20190823
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 38
IP  - 5
DP  - 2003 Nov
TI  - Neutropenia impairs venous thrombosis resolution in the rat.
PG  - 1090-8
AB  - OBJECTIVES: Neutrophil influx is one of the first events in a formed deep venous 
      thrombosis (DVT), but whether these cells are active participants in the 
      resolution process is not clear. This study tests the hypothesis that neutrophils 
      (PMN) are active participants in DVT resolution. METHODS: Thrombosis was induced 
      by inferior vena caval (IVC) ligation in male Sprague-Dawley rats, and rats were 
      sacrificed at 2, 4, or 7 days for evaluation of the thrombus. Neutropenia was 
      induced by rabbit anti-rat PMN serum, and controls received rabbit serum. 
      Venography was performed at the 7-day time point. Immunohistochemical staining 
      was performed to quantify intrathrombus PMNs and monocytes, and the 
      myeloperoxidase (MPO) assay was performed to assess intrathrombus neutrophil 
      activity. Intrathrombus concentrations of kerotinocyte cytokine (KC), macrophage 
      inflammatory protein-2 (MIP-2), gamma interferon inducible protein-10 (IP-10), 
      macrophage inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant 
      protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha were quantified by 
      enzyme immunoassay at each time point and normalized to total protein. Total 
      collagen was determined at day 7. RESULTS: Peripheral blood smears showed a 94% 
      PMN reduction at 2 days (P <.05), recovering to 44% of control at 7 days. 
      Intrathrombus PMNs were significantly lower in neutropenic rats at 2 and 4 days, 
      but there were no differences in intrathrombus monocytes. The MPO assay confirmed 
      reduced neutrophil activity at 4 days. Thrombi from neutropenic rats were larger 
      at 2 and 7 days compared with controls. In vivo thrombus area at 7 days as 
      assessed by venography was also greater in neutropenic rats as compared with 
      controls. The intrathrombus KC concentration was increased more than 20-fold in 
      the neutropenic rats at 2 days, but there were no significant differences in 
      other intrathrombus chemokines. Finally, intrathrombus collagen was increased 
      over threefold in neutropenic rats as compared with controls. CONCLUSION: 
      Neutropenia impairs DVT resolution by several measures, most likely by altering 
      normal fibrinolytic activity and thrombus collagen turnover.
FAU - Varma, Manu R
AU  - Varma MR
AD  - Department of Surgery, University of Michigan Medical School, Ann Arbor, 48109, 
      USA.
FAU - Varga, Andrea J
AU  - Varga AJ
FAU - Knipp, Brian S
AU  - Knipp BS
FAU - Sukheepod, Pasu
AU  - Sukheepod P
FAU - Upchurch, Gilbert R
AU  - Upchurch GR
FAU - Kunkel, Steven L
AU  - Kunkel SL
FAU - Wakefield, Thomas W
AU  - Wakefield TW
FAU - Henke, Peter K
AU  - Henke PK
LA  - eng
GR  - HL 63148/HL/NHLBI NIH HHS/United States
GR  - HL 69780/HL/NHLBI NIH HHS/United States
GR  - K08 HL 67885/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (Chemokines)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Chemokines/immunology
MH  - Collagen/immunology
MH  - Fibrinolysis/physiology
MH  - Male
MH  - Neutropenia/*immunology/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function/physiology
MH  - Remission, Spontaneous
MH  - Thrombosis/immunology/*physiopathology
MH  - Venous Thrombosis/*immunology/*physiopathology
EDAT- 2003/11/07 05:00
MHDA- 2003/12/05 05:00
CRDT- 2003/11/07 05:00
PHST- 2003/11/07 05:00 [pubmed]
PHST- 2003/12/05 05:00 [medline]
PHST- 2003/11/07 05:00 [entrez]
AID - S0741521403004312 [pii]
AID - 10.1016/s0741-5214(03)00431-2 [doi]
PST - ppublish
SO  - J Vasc Surg. 2003 Nov;38(5):1090-8. doi: 10.1016/s0741-5214(03)00431-2.