Lactoferrin is a prominent component of neutrophil secondary granules and can be released when neutrophils are activated. The concentration of lactoferrin in blood has been demonstrated to be increased in certain inflammatory diseases. In contrast to a well described biochemical characterization of lactoferrin as an iron-binding protein, its physiological role in the regulation of inflammation and other host defense mechanisms is unclear. The current proposed study will test three hypotheses: (i) lactoferrin derived from neutrophils is an important physiological mediator in the down-regulation of blood anticoagulation; (ii) the significant elevation of lactoferrin in blood, or at sites of inflammation can contribute significantly to the development of prothrombotic sequelae as seen in the disseminated intravascular coagulation (DIC) associated with bacterial infections; and (iii) the structural determinant(s) of lactoferrin involved in heparin binding is located within a specific sequence (residues 25-31) of the N-terminus. Thus, specific aims of this proposal are: (1) to determine the relationship between the elevation of plasma lactoferrin and the development of prothrombotic complications in patients with bacterial infections. The plasma lactoferrin concentration in patients with DIC resulting from different underlying diseases or with different inflammatory diseases will be examined; (2) to define the structural determinant(s) of lactoferrin involved in heparin binding. Both site- specific and domain-replacement mutagenesis will be used to determine the contribution of N-terminal basic residues (25 to 31) in heparin binding; (3) to study the activity of lactoferrin in the regulation of protein C anticoagulant pathway. Both the effect of lactoferrin on the generation of activated protein C and the specific binding of lactoferrin to chondroitin sulfate moiety of thrombomodulin will be examined. The completion of these studies will enable us to understand the biological role of lactoferrin in the regulation of inflammation and blood coagulation, and will provide new scientific background for the clinical evaluation and management of infectious diseases with thrombotic complications.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CCT-L (O1))
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Mondoro, Traci
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Ohio State University
Schools of Medicine
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Yang, Shangbin; Jin, Ming; Lin, Shili et al. (2011) ADAMTS13 activity and antigen during therapy and follow-up of patients with idiopathic thrombotic thrombocytopenic purpura: correlation with clinical outcome. Haematologica 96:1521-7
Hofmeister, Craig C; Jin, Ming; Cataland, Spero R et al. (2010) TTP disease course is independent of myeloma treatment and response. Am J Hematol 85:304-6
Wu, Haifeng M; Xu, Lihui; Sedmak, Daniel D et al. (2010) Personalized healthcare in clotting disorders. Per Med 7:65-73
Cataland, Spero R; Yang, Shang-bin; Witkoff, Leslie et al. (2009) Demographic and ADAMTS13 biomarker data as predictors of early recurrences of idiopathic thrombotic thrombocytopenic purpura. Eur J Haematol 83:559-64
Cataland, Spero R; Jin, Ming; Lin, Shili et al. (2008) Effect of prophylactic cyclosporine therapy on ADAMTS13 biomarkers in patients with idiopathic thrombotic thrombocytopenic purpura. Am J Hematol 83:911-5
Jin, Ming; Casper, T Charles; Cataland, Spero R et al. (2008) Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. Br J Haematol 141:651-8
Cataland, Spero R; Jin, Ming; Lin, Shili et al. (2007) Cyclosporin and plasma exchange in thrombotic thrombocytopenic purpura: long-term follow-up with serial analysis of ADAMTS13 activity. Br J Haematol 139:486-93
Cataland, Spero R; Wu, Haifeng M (2007) Targeting the inhibitor of ADAMTS13 in thrombotic thrombocytopenic purpura. Expert Opin Pharmacother 8:437-44
Cataland, Spero R; Jin, Ming; Ferketich, Amy K et al. (2007) An evaluation of cyclosporin and corticosteroids individually as adjuncts to plasma exchange in the treatment of thrombotic thrombocytopenic purpura. Br J Haematol 136:146-9
Cataland, S R; Jin, M; Smith, E et al. (2006) Full evaluation of an acquired case of thrombotic thrombocytopenic purpura following the surgical resection of glioblastoma multiforme. J Thromb Haemost 4:2733-7

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