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Serpins pp 157-182 | Cite as

Analysis of In Vivo Serpin Functions in Models of Inflammatory Vascular Disease

  • Hao Chen
  • Sriram Ambadapadi
  • Erbin Dai
  • Liying Liu
  • Jordan R. Yaron
  • Liqiang Zhang
  • Alexandra Lucas
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1826)

Abstract

Serpins have a wide range of functions in regulation of serine proteases in the thrombotic cascade and in immune responses, representing up to 2–10% of circulating proteins in the blood. Selected serpins also have cross-class inhibitory actions for cysteine proteases in inflammasome and apoptosis pathways. The arterial and venous systems transport blood throughout the mammalian body representing a central site for interactions between coagulation proteases and circulating blood cells (immune cells) and target tissues, a very extensive and complex interaction. While analysis of serpin functions in vitro in kinetics or gel shift assays or in tissue culture provides very necessary information on molecular mechanisms, the penultimate assessment of biological or physiological functions and efficacy for serpins as therapeutics requires study in vivo in whole animal models (some also consider cell culture to be an in vivo approach).

Mouse models of arterial transplant with immune rejection as well as models of inflammatory vasculitis induced by infection have been used to study the interplay between the coagulation and immune response pathways. We describe here three in vivo vasculitis models that are used to study the roles of serpins in disease and as therapeutics. The models described include (1) mouse aortic allograft transplantation, (2) human temporal artery (TA) xenograft into immunodeficient mouse aorta, and (3) mouse herpes virus (MHV68)-induced inflammatory vasculitis in interferon-gamma receptor (IFNγR) knockout mice.

Key words

Serpin Thrombosis Thrombolysis Inflammation Immune Serine protease Cysteine protease Vasculitis Virus Transplant 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hao Chen
    • 1
    • 2
  • Sriram Ambadapadi
    • 3
    • 4
  • Erbin Dai
    • 5
  • Liying Liu
    • 5
  • Jordan R. Yaron
    • 6
  • Liqiang Zhang
    • 3
  • Alexandra Lucas
    • 3
    • 4
  1. 1.The Department of Tumor SurgerySecond Hospital of Lanzhou UniversityLanzhouChina
  2. 2.The Key Laboratory of the Digestive System Tumors of Gansu ProvinceLanzhouChina
  3. 3.Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign InstituteArizona State UniversityTempeUSA
  4. 4.Department of Medicine, Divisions of Cardiovascular Medicine and RheumatologyUniversity of FloridaGainesvilleUSA
  5. 5.Department of SurgeryBIDMC, Harvard Medical SchoolBostonUSA
  6. 6.Centers for Personalized Diagnostics and Immunology, Vaccines and Virotherapy, Biodesign InstituteArizona State UniversityTempeUSA

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