title: Platelets inhibit the lysis of pulmonary microemboli.
abstract: Using tracings of (125)I-labeled fibrin(ogen) in rodents, we examined the hypothesis that platelets impede the lysis of pulmonary emboli. (125)I-Microemboli (ME, 3-10 micron diameter) lodged homogeneously throughout the lungs after intravenous injection in both rats and mice (60% of injected dose), caused no lethality, and underwent spontaneous dissolution (50 and 100% within 1 and 5 h, respectively). Although lung homogenates displayed the most intense fibrinolytic activity of all the major organs, dissolution of ME was much slower in isolated perfused lungs (IPL) than was observed in vivo. Addition of rat plasma to the perfusate facilitated ME dissolution in IPL to a greater extent than did addition of tissue-type plasminogen activator alone, suggesting that permeation of the clot by plasminogen is the rate-limited step in lysis. Platelet-containing ME injected in rats lysed much more slowly than did ME formed from fibrin alone. (125)I-Thrombi, formed in the pulmonary vasculature of mice in response to intravascular activation of platelets by injection of collagen and epinephrine, were essentially resistant to spontaneous dissolution. Moreover, injection of the antiplatelet glycoprotein IIb/IIIa antibody 7E3 F(ab')(2) facilitated spontaneous dissolution of pulmonary ME and augmented fibrinolysis by a marginally effective dose of Retavase (10 microg/kg) in rats. These studies show that platelets suppress pulmonary fibrinolysis. The mechanism(s) by which platelets stabilize ME and utility of platelet inhibitors to facilitate their dissolution deserves further study.
authors.affiliation: Institute for Environmental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Murciano
authors.forename: David
authors.initials: D
authors.lastname: Harshaw
authors.forename: David G
authors.initials: DG
authors.lastname: Neschis
authors.forename: Lauren
authors.initials: L
authors.lastname: Koniaris
authors.forename: Khalil
authors.initials: K
authors.lastname: Bdeir
authors.forename: Sandra
authors.initials: S
authors.lastname: Medinilla
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
authors.forename: Michael A
authors.initials: MA
authors.lastname: Golden
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
authors.forename: Marian T
authors.initials: MT
authors.lastname: Nakada
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001790:Blood Physiological Phenomena; D001792:Blood Platelets / Q000502:physiology*; D005342:Fibrinolysis / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010477:Perfusion; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D011655:Pulmonary Embolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010959:Tissue Plasminogen Activator