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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN

Location: Children's Nutrition Research Center

Title: Endothelial-derived GM-CSF influences expression of oncostatin M

Authors
item Elbjeirami, Wafa -
item Donnachie, Elizabeth -
item Burns, Alan -
item Smith, C -

Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 15, 2011
Publication Date: October 1, 2011
Citation: Elbjeirami, W.M., Donnachie, E.M., Burns, A.R., Smith, C.W. 2011. Endothelial-derived GM-CSF influences expression of oncostatin M. American Journal of Physiology - Cell Physiology. 301(4):C947-C953.

Interpretive Summary: These studies were designed to understand how some white blood cells contribute to inflammation when they migrate from the blood into body tissues. We studied these cells that mimicked the natural ways that white blood cells migrate into body tissues. We found that the white blood cells released a hormone-like factor (a protein) at the time they migrate into tissue. This protein is known to increase inflammation, and this study is the first to show that it is released from white blood cells at the time it migrates into the body's tissues. This new information will be important in long term studies of the role nutrition plays in promoting or reducing inflammation.

Technical Abstract: During and following transendothelial migration, neutrophils undergo a number of phenotypic changes resulting from encounters with endothelial-derived factors. This report uses an in vitro model with HUVEC and isolated human neutrophils to examine the effects of two locally-derived cytokines, granulocyte-macrophage stimulating factor (GM-CSF) and colony-stimulating factor (CSF) on oncostatin M (OSM) expression. Neutrophils contacting activated HUVEC expressed and released increased amounts of oncostatin M (OSM), a proinflammatory cytokine known to induce PMN adhesion and chemotaxis. Neutrophil transendothelial migration resulted in three fold higher OSM expression and protein levels compared to non-transmigrated cells. Addition of anti-GM-CSF neutralizing antibody reduced OSM expression level but anti-G-CSF was without effect. GM-CSF but not G-CSF protein addition to cultures of isolated neutrophils resulted in a significant increase in OSM protein secretion. However, inhibition of beta2 integrins by neutralizing antibody significantly reduced GM-CSF-induced OSM production indicating this phenomenon is adhesion dependent. Thus, cytokine-stimulated EC can produce sufficient quantities of GM-CSF to influence in an adhesion dependent manner the phenotypic characteristics of neutrophils resulting in the latter's transmigration. Both transmigration and adhesion phenomenon lead to increased production of OSM by neutrophils which then play a major role in inflammatory response.

Last Modified: 9/10/2014
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