Advisory Committee Chair
Louis B Justement
Advisory Committee Members
David E Briles
Suzanne M Michalek
Chander Raman
Chad Steele
Document Type
Dissertation
Date of Award
2011
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
TLT2 is one of four receptors conserved between mouse and human within the TREM locus, and is expressed on B cells, macrophages, and neutrophils. TLT2 ligation on murine macrophages induces the production of chemokines and growth factors, as evidenced by ex vivo treatment with anti-TLT2 mAbs. This treatment did not lead to the upregulation of activation markers such as CD69 or costimulatory molecules such as CD80 and CD86, indicating a specific response following TLT2 ligation. This is recapitulated in vivo following injection of anti-TLT2 mAbs resulting in the production of chemokines and growth factors, which ultimately lead to enhanced neutrophil recruitment. Ligation of TLT2 on murine neutrophils results in an enhanced respiratory burst, as well as potentiation of degranulation and chemotaxis in response to agonists that bind G protein-coupled receptors (GPCRs), including FMLP, KC, MIP-2, IL-8, and C5a. However, the neutrophil responses to GM-CSF, LPS, and FcR ligation were unaltered, suggesting that TLT2 specifically potentiates the neutrophil response to signals derived from GPCRs. Administration of anti-TLT2 mAb results in enhanced neutrophil accumulation in response to nonspecific inflammatory mediators in vivo, and competitive adoptive transfer experiments demonstrate enhanced recruitment of anti-TLT2 mAb treated neutrophils compared to control neutrophils in response to lung inflammation. These results demonstrate that TLT2 regulates an intricate feed-forward loop, wherein it is important for driving the production of factors that recruit neutrophils, as well as enhancing the response of neutrophils towards chemokines and bacterial products that signal via GPCRs.
Recommended Citation
Halpert, Matthew Martin, "Determining the functional role of TREM-like transcript 2 in the innate immune response" (2011). All ETDs from UAB. 1845.
https://digitalcommons.library.uab.edu/etd-collection/1845