PMID- 11815383
OWN - NLM
STAT- MEDLINE
DCOM- 20020402
LR  - 20240322
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 135
IP  - 2
DP  - 2002 Jan
TI  - The effects of heparin and related molecules on vascular permeability and 
      neutrophil accumulation in rabbit skin.
PG  - 469-79
AB  - Unfractionated heparin (UH) has been shown to possess a wide range of properties 
      which are potentially anti-inflammatory. Many of these studies, including effects 
      of heparin on adhesion of inflammatory cells to endothelium, have been carried 
      out in vitro. In the present study, we have used radioisotopic techniques to 
      study the effect of UH, and related molecules, on in vivo inflammatory responses 
      (plasma exudation (PE) and PMN accumulation) in rabbit skin induced by cationic 
      proteins, mediators and antigen. Intradermal (i.d.) pretreatment with UH 
      dose-dependently inhibited poly-L-lysine (PLL)-induced responses. The same 
      treatment had no effect on antigen (extract of Alternaria tenuis, AT)-, 
      formyl-methionyl-leucyl-phenylalanine (fMLP)- or leukotriene (LT) B(4)-induced 
      responses, although i.d. dextran sulphate (DS) significantly inhibited responses 
      to all of these mediators. High dose (10,000 u kg(-1)) intravenous UH 
      significantly decreased cutaneous responses to fMLP and LTB(4). By comparison, 
      the selectin inhibitor, fucoidin, and DS, were very effective inhibitors of these 
      responses, and of responses to AT and PLL. In contrast to the weak effect in the 
      in vivo studies, UH significantly inhibited in vitro homotypic aggregation of 
      rabbit PMNs, showing that it can modify PMN function. Our data with i.d. UH 
      confirm the important ability of this molecule to interact with and neutralize 
      polycationic peptides in vivo, suggesting that this is a prime role of endogenous 
      heparin. The lack of effect of exogenous heparin on acute inflammatory responses 
      induced by allergen, suggests that cationic proteins are unlikely to be primary 
      mediators of the allergen-induced PE or PMN accumulation.
FAU - Jones, Helen
AU  - Jones H
AD  - Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, 
      5th Floor Hodgkin Building, King's College London, Guy's Campus, London SE1 9RT. 
      helenie.jones@kcl.ac.uk
FAU - Paul, William
AU  - Paul W
FAU - Page, Clive P
AU  - Page CP
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Capillary Permeability/*drug effects/physiology
MH  - Cell Movement/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Heparin/*pharmacology
MH  - Injections, Intradermal
MH  - Male
MH  - Neutrophils/*cytology/*drug effects
MH  - Rabbits
MH  - Skin/cytology/*drug effects/metabolism
PMC - PMC1573160
EDAT- 2002/01/30 10:00
MHDA- 2002/04/03 10:01
PMCR- 2003/01/01
CRDT- 2002/01/30 10:00
PHST- 2002/01/30 10:00 [pubmed]
PHST- 2002/04/03 10:01 [medline]
PHST- 2002/01/30 10:00 [entrez]
PHST- 2003/01/01 00:00 [pmc-release]
AID - 0704505 [pii]
AID - 10.1038/sj.bjp.0704505 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2002 Jan;135(2):469-79. doi: 10.1038/sj.bjp.0704505.