Biomaterial Database

Transepithelial migration of neutrophils into the lung requires TREM-1. 2013

Julia Klesney-Tait, and Kathy Keck, and Xiaopeng Li, and Susan Gilfillan, and Karel Otero, and Sankar Baruah, and David K Meyerholz, and Steven M Varga, and Cory J Knudson, and Thomas O Moninger, and Jessica Moreland, and Joseph Zabner, and Marco Colonna

Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 200 Hawkins Dr., Iowa City, Iowa 52242, USA. juliaklesney-tait@uiowa.edu

Acute respiratory infections are responsible for more than 4 million deaths each year. Neutrophils play an essential role in the innate immune response to lung infection. These cells have an armamentarium of pattern recognition molecules and antimicrobial agents that identify and eliminate pathogens. In the setting of infection, neutrophil triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory signaling. Here we demonstrate for the first time that TREM-1 also plays an important role in transepithelial migration of neutrophils into the airspace. We developed a TREM-1/3-deficient mouse model of pneumonia and found that absence of TREM-1/3 markedly increased mortality following Pseudomonas aeruginosa challenge. Unexpectedly, TREM-1/3 deficiency resulted in increased local and systemic cytokine production. TREM-1/3-deficient neutrophils demonstrated intact bacterial killing, phagocytosis, and chemotaxis; however, histologic examination of TREM-1/3-deficient lungs revealed decreased neutrophil infiltration of the airways. TREM-1/3-deficient neutrophils effectively migrated across primary endothelial cell monolayers but failed to migrate across primary airway epithelia grown at the air-liquid interface. These data define a new function for TREM-1 in neutrophil migration across airway epithelial cells and suggest that it amplifies inflammation through targeted neutrophil migration into the lung.

UI	MeSH Term	Description	Entries
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011550	Pseudomonas aeruginosa	A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.	Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D011552	Pseudomonas Infections	Infections with bacteria of the genus PSEUDOMONAS.	Infections, Pseudomonas,Pseudomonas aeruginosa Infection,Infection, Pseudomonas,Pseudomonas Infection,Pseudomonas aeruginosa Infections
D011971	Receptors, Immunologic	Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.	Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D000073871	Triggering Receptor Expressed on Myeloid Cells-1	An approximately 230 amino acid membrane glycoprotein characterized by an IMMUNOGLOBULIN V-SET DOMAIN in its N-terminal half. It is expressed by MONOCYTES and NEUTROPHILS in response to INFLAMMATION related to bacterial and fungal infections. It triggers the release of pro-inflammatory CHEMOKINES; CYTOKINES, and expression of cell activation markers and is a critical regulator of SEPTIC SHOCK.	CD354 Antigen,TREM-1 Protein,Antigen, CD354,TREM 1 Protein,Triggering Receptor Expressed on Myeloid Cells 1
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D057705	Transendothelial and Transepithelial Migration	The passage of cells across the layer of ENDOTHELIAL CELLS, i.e., the ENDOTHELIUM; or across the layer of EPITHELIAL CELLS, i.e. the EPITHELIUM.	Transendothelial Migration,Diapedesis,Endothelial Transmigration,Transepithelial Migration,Transepithelial and Transendothelial Migration,Migration, Transendothelial,Migration, Transepithelial,Transmigration, Endothelial