Abstract

During the resolution of inflammation, some monocytes can migrate from the blood into lymphatic vessels via a process termed reverse transmigration. This transmigration can trigger the differentiation of blood monocytes into dendritic cells (DC). In contrast, monocytes that remain in the subendothelium become macrophages. The investigator has modeled this process in vitro through the use of endothelial cell monolayers which are cultured on an underlying collagen matrix. Preliminary studies from the investigator's laboratory have begun to characterize this mutually exclusive differentiation process, and to examine the roles of the transmembrane transporter proteins p-glycoprotein/MDR-1 and MRP on this process. These studies have led to the hypothesis that antagonism of MDR-1, promotes the development of monocytes into macrophages, which concomitantly prevents the differentiation of monocytes into DC and the migration of DC out of the tissues. Furthermore, MRP may transport an arachidonate metabolite, possibly LTC4, that directly participates in the migration and maturation of DC. This new application from a new investigator has 3 specific aims.
The first aim will identify the factors that induce monocytes to become DC in the in vitro model system.
The second aim will determine whether all monocytes, or just a subset of cells, have the capacity to differentiate into DC.
The third aim will explore the roles of the transmembrane transporter proteins in DC migration and maturation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049653-04
Application #
6650791
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Johnson, David R
Project Start
2000-09-15
Project End
2004-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$254,250
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Williams, Jesse W; Martel, Catherine; Potteaux, Stephane et al. (2018) Limited Macrophage Positional Dynamics in Progressing or Regressing Murine Atherosclerotic Plaques-Brief Report. Arterioscler Thromb Vasc Biol 38:1702-1710
Randolph, Gwendalyn J; Ivanov, Stoyan; Zinselmeyer, Bernd H et al. (2017) The Lymphatic System: Integral Roles in Immunity. Annu Rev Immunol 35:31-52
Cifarelli, Vincenza; Ivanov, Stoyan; Xie, Yan et al. (2017) CD36 deficiency impairs the small intestinal barrier and induces subclinical inflammation in mice. Cell Mol Gastroenterol Hepatol 3:82-98
Ivanov, Stoyan; Randolph, Gwendalyn J (2017) Myeloid cells pave the way for lymphatic system development and maintenance. Pflugers Arch 469:465-472
Ivanov, Stoyan; Scallan, Joshua P; Kim, Ki-Wook et al. (2016) CCR7 and IRF4-dependent dendritic cells regulate lymphatic collecting vessel permeability. J Clin Invest 126:1581-91
Lu, Qun; Yokoyama, Christine C; Williams, Jesse W et al. (2016) Homeostatic Control of Innate Lung Inflammation by Vici Syndrome Gene Epg5 and Additional Autophagy Genes Promotes Influenza Pathogenesis. Cell Host Microbe 19:102-13
Durai, Vivek; Murphy, Kenneth M (2016) Functions of Murine Dendritic Cells. Immunity 45:719-736
Wu, Xiaodi; Briseño, Carlos G; Durai, Vivek et al. (2016) Mafb lineage tracing to distinguish macrophages from other immune lineages reveals dual identity of Langerhans cells. J Exp Med 213:2553-2565
Kim, Ki-Wook; Williams, Jesse W; Wang, Ya-Ting et al. (2016) MHC II+ resident peritoneal and pleural macrophages rely on IRF4 for development from circulating monocytes. J Exp Med 213:1951-9
Bagaitkar, Juhi; Pech, Nancy K; Ivanov, Stoyan et al. (2015) NADPH oxidase controls neutrophilic response to sterile inflammation in mice by regulating the IL-1?/G-CSF axis. Blood 126:2724-33

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