PMID- 15951297
OWN - NLM
STAT- MEDLINE
DCOM- 20060810
LR  - 20171116
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Linking)
VI  - 90
IP  - 6
DP  - 2005 Jun
TI  - Prevention of platelet-polymorphonuclear leukocyte interactions: new clues to the 
      antithrombotic properties of parnaparin, a low molecular weight heparin.
PG  - 833-9
AB  - BACKGROUND AND OBJECTIVES: Heparin might possess anti-thrombotic properties other 
      than anticoagulation. The aim of the present study was to test the effects of a 
      low-molecular weight heparin, parnaparin, on adhesive molecule-mediated 
      platelet-polymorphonuclear (PMN) leukocyte interactions and on PMN function. 
      DESIGN AND METHODS: Platelets and PMN were isolated from citrated blood from 
      healthy subjects. Pre-activated platelets incubated with PMN under dynamic 
      conditions formed mixed cell aggregates. In previous experiments PMN were 
      stimulated in vitro by purified P-selectin or 
      formyl-methionyl-leucyl-phenylalanine (fMLP). Dual color flow cytometry was used 
      to detect the formation of platelet-PMN mixed cell aggregates, and PMN activation 
      was tested for by measuring L-selectin shedding, tissue factor expression and PMN 
      degranulation. The effect of parnaparin was compared to that of unfractionated 
      heparin. RESULTS: Parnaparin, at a concentration of 0.3-0.8 IUaXa/mL, inhibited 
      the formation of mixed cell aggregates (48.8+/-9.7% of total PMN population) by 
      up to 60% in a concentration-dependent manner, while heparin inhibited 
      aggregation up to 40%. Parnaparin, (0.3-0.8 IUaXa/mL), prevented L-selectin 
      shedding from PMN, which was induced by purified P-selectin (5 mg/mL) or fMLP 
      (0.5 mmol/L) by 65% and 67%, respectively. Inhibition was independent of 
      incubation time (5-20 min). Parnaparin (0.8 IUaXa/mL) also inhibited tissue 
      factor expression on PMN (% of positive cells), which was induced by P-selectin 
      or fMLP (185+/-10 and 241+/-80% of basal value, respectively). Parnaparin 
      protected PMN from degranulation after challenge with either stimulus (>95% 
      inhibition). All the effects of parnaparin were observed with heparin at similar 
      concentrations, although to a lesser extent and were often not significantly 
      different from events in controls. INTERPRETATION AND CONCLUSIONS: In conclusion, 
      the process of depolymerization of heparin to obtain low molecular weight 
      parnaparin resulted in an increased, anticoagulant-independent effect on PMN 
      function. Thus, the overall anti-thrombotic properties of parnaparin may be 
      partly due to a leukocyte-mediated anti-inflammatory effect.
FAU - Maugeri, Norma
AU  - Maugeri N
AD  - Research Laboratories, Center for High Technology Research and Education in 
      Biomedical Sciences, Catholic University, Campobasso, Italy. 
      normamaugeri2003@yahoo.it
FAU - de Gaetano, Giovanni
AU  - de Gaetano G
FAU - Barbanti, Miriam
AU  - Barbanti M
FAU - Donati, Maria Benedetta
AU  - Donati MB
FAU - Cerletti, Chiara
AU  - Cerletti C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (P-Selectin)
RN  - 126880-86-2 (L-Selectin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 9005-49-6 (Heparin)
RN  - M316WT19D8 (parnaparin)
SB  - IM
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Blood Platelets/*cytology
MH  - Cell Adhesion
MH  - Fibrinolytic Agents/*pharmacology
MH  - Flow Cytometry
MH  - Heparin/chemistry
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Humans
MH  - L-Selectin/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*cytology
MH  - P-Selectin/metabolism
MH  - Platelet Activation
MH  - Time Factors
EDAT- 2005/06/14 09:00
MHDA- 2006/08/11 09:00
CRDT- 2005/06/14 09:00
PHST- 2005/06/14 09:00 [pubmed]
PHST- 2006/08/11 09:00 [medline]
PHST- 2005/06/14 09:00 [entrez]
PST - ppublish
SO  - Haematologica. 2005 Jun;90(6):833-9.