title: Heparin Interaction with the Primed Polymorphonuclear Leukocyte CD11b Induces Apoptosis and Prevents Cell Activation.
abstract: Heparin is known to have anti-inflammatory effects, yet the mechanisms are not completely understood. In this study, we tested the hypothesis that heparin has a direct effect on activated polymorphonuclear leukocytes (PMNLs), changing their activation state, and can explain its anti-inflammatory effect. To test our hypothesis, we designed both in vitro and ex vivo studies to elucidate the mechanism by which heparin modulates PMNL functions and therefore the inflammatory response. We specifically tested the hypothesis that priming of PMNLs renders them more susceptible to heparin. Amplified levels of CD11b and increased rate of superoxide release manifested PMNL priming. Increase in cell priming resulted in a dose-dependent increase in heparin binding to PMNLs followed by augmented apoptosis. Blocking antibodies to CD11b inhibited heparin binding and abolished the apoptotic response. Moreover, heparin caused a significant dose-dependent decrease in the rate of superoxide release from PMNLs, which was blunted by blocking antibodies to CD11b. Altogether, this study shows that the interaction of heparin with the PMNL CD11b results in cell apoptosis and explains heparin's anti-inflammatory effects.
authors.affiliation: Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel; Technion Faculty of Medicine, 3525433 Haifa, Israel.
authors.forename: Meital
authors.initials: M
authors.lastname: Cohen-Mazor
authors.affiliation: Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel; Technion Faculty of Medicine, 3525433 Haifa, Israel.
authors.forename: Rafi
authors.initials: R
authors.lastname: Mazor
authors.affiliation: Technion Faculty of Medicine, 3525433 Haifa, Israel; Department of Nephrology and Hypertension, Western Galilee Hospital, 22100 Nahariya, Israel.
authors.forename: Batya
authors.initials: B
authors.lastname: Kristal
authors.affiliation: Department of Anesthesiology & Critical Care, VA San Diego Healthcare System, San Diego, CA 92161, USA.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Kistler
authors.affiliation: Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel; Technion Faculty of Medicine, 3525433 Haifa, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Ziv
authors.affiliation: Hematology Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel.
authors.forename: Judith
authors.initials: J
authors.lastname: Chezar
authors.affiliation: Eliachar Research Laboratory, Western Galilee Hospital, 22100 Nahariya, Israel; Technion Faculty of Medicine, 3525433 Haifa, Israel.
authors.forename: Shifra
authors.initials: S
authors.lastname: Sela
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019138:Antibodies, Blocking / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D019138:Antibodies, Blocking; D039481:CD11b Antigen; D013481:Superoxides; D006493:Heparin
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