title: Locally available heparin modulates inflammatory cell recruitment in a manner independent of anticoagulant activity.
abstract: Heparin is known to possess anti-inflammatory properties that in many cases appear to be separable from its anticoagulant activity. Mast cells, located in tissue, are the sole source of endogenous heparin, which may be involved in control of the inflammatory response. The majority of studies of the effects of heparin on the inflammatory response, carried out to date, have involved systemic administration and the potential influence of heparin in the site of inflammation has been less clear. In the present study, the effects of locally administered heparin and a non-anticoagulant derivative were investigated on leucocyte accumulation in the inflamed peritoneal cavity and leucocyte-endothelial interactions in the mesenteric microcirculation of the rat. Heparin and non-anticoagulant heparin inhibited the influx of neutrophils to the site of inflammation, as well as leucocyte rolling and adhesion in post-capillary venules. These effects were apparent only while heparin was present in the peritoneal cavity and plasma and may reflect, in part, an action on resident peritoneal cells, as the heparins tested were found also to inhibit the expression of endothelial adhesion molecules in response to products of activated mononuclear cells, in vitro. Our data show that locally administered heparin has anti-inflammatory effects in an in vivo model of peritoneal inflammation whilst present at the site of inflammation. These non-anticoagulant properties may involve interaction with cells in the site of inflammation, in addition to inhibiting cell adhesion at the level of the microcirculation.
authors.affiliation: Department of Pharmacology, The School of Pharmacy, University of London, 29-39, Brunswick Square, London, WC1N 1AX, United Kingdom. rebecca.lever@pharmacy.ac.uk <rebecca.lever@pharmacy.ac.uk>
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lever
authors.forename: Amir
authors.initials: A
authors.lastname: Smailbegovic
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism* / Q000494:pharmacology; D000925:Anticoagulants / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D006493:Heparin