Target siglecs to treat lung inflammation

LID-PEG Project 1 will test a major hypothesis of the Program: Treatment with enhanced multivalent siglec ligands will limit lung inflammation.

Asthma typically involves eosinophilic lung inflammation, whereas COPD is associated with neutrophilic lung inflammation. The study of natural cellular and molecular processes that limit lung inflammation may reveal new and effective therapies for these diseases. Siglec-8 and Siglec-9 are members of the sialic acid-binding immunoglobulin-like lectin (siglec) family found on non-overlapping cell subsets, with Siglec-8 expressed on human eosinophils, mast cells and basophils, and Siglec-9 expressed on neutrophils, macrophages, NK cells and some B and T cells. These transmembrane proteins have extracellular binding domains that recognize similar, but distinct glycan ligands (6’-sulfo sialyl Lewis X for Siglec-8 and 6-sulfo sialyl Lewis X for Siglec-9). Engagement of Siglec-8 or Siglec-9 with antibodies and/or artificial ligands causes eosinophil and neutrophil death, respectively. The overall goal of this project is to exploit eosinophil and neutrophil siglecs to treat lung inflammation by inducing inflammatory cell death. Siglec-8 and Siglec-9 provide a novel means to target and deplete eosinophils and neutrophils.

Dr. Bruce Bochner is a physician-scientist and immunologist. His translational research revealed new mechanisms of allergic and pulmonary inflammation. Working with primary human cells and tissues and relevant animal models, his research team identified targets for the development of new therapies. He has effectively incorporated glycobiology into his biomedical research program for >20 years.

 

Bruce S. Bochner

  • Professor of Medicine
    Northwestern University
    Feinberg School of Medicine
    Division of Allergy-Immunology
    240 E. Huron St, Room M-306 Chicago, IL 60611
  • Phone: 312-503-0068
    Email: bruce.bochner@northwestern.edu
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