Neutrophils and deep venous thrombosis.
A case can be made for the participation of polymorphonuclears (PMN) in the initiation and propagation of venous thrombosis. In animal models leukocytes adhered to areas of veins that serve as sites for initiation of thrombi in patients. In addition, PMN are found in white layers of thrombin where they may interact with platelets to attract more of each. This would add bulk and promote coagulation so that red layers are formed. Lidocaine and one of its derivatives inhibited leukocyte adhesion to veins in dogs and lidocaine reduced the incidence of deep venous thrombosis (DVT) in patients after hip replacement, suggesting but not proving that inhibition of PMN adhesion might have contributed. A new approach for preventing PMN contribution to DVT is suggested by recent studies which identified three families of adhesive receptors (integrins, intercellular adhesion molecules and selectins) on endothelium, leukocytes and platelets. Monoclonal antibodies against beta 2-integrins on leukocytes reduced leukocyte adhesion, emigration and PMN-dependent tissue injury in infection, inflammation and ischemia-reperfusion injury in animals. Selectins bind to specific carbohydrate ligands containing sialylated Lewis X, suggesting that relatively small analogues might inhibit PMN adhesion. Both platelets and PMN adhere to polymerizing fibrin through undefined mechanisms. Inhibition of this process might inhibit the buildup of white layers of thrombi.
Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pa 19140.
G J
GJ
Stewart
D000818:Animals; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000502:physiology; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D015539:Platelet Activation; D011817:Rabbits; D013924:Thrombophlebitis / Q000503:physiopathology* / Q000517:prevention & control
D015815:Cell Adhesion Molecules; D016023:Integrins