Mathematical modeling supports the presence of neutrophil depriming in vivo. Issue 3 (3rd March 2014)

• Record Type: Journal Article
• Authors: Summers, Charlotte; Chilvers, Edwin R.; Peters, A Michael
• Is Part Of: Physiological reports. Volume 2:Issue 3(2014:Mar.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2014-03-03
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.1002/phy2.241
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy2241-abs-0001"> <title>Abstract</title> <p>Following migration into the intestinal mucosa in inflammatory bowel disease (IBD), neutrophils enter the intestinal lumen and are excreted. This provides a basis for quantification of disease activity by measuring excreted label following injection of In‐111‐labeled neutrophils. In severe pan‐colitis, 50% of the injected In‐111 is typically recovered in the feces, indicating that 50% of neutrophil turnover is via fecal excretion. Neutrophils have an intravascular lifespan of ~10 h and a distribution volume of ~10 L, so total body neutrophil turnover is 10.<italic>N</italic>/10 cells/h, where <italic>N</italic> is the peripheral blood neutrophil count (cells/L). Neutrophil loss via the colon in a patient with 50% fecal In‐111 loss is therefore <italic>N</italic>/120 cells/min. Pan‐colonic mucosal‐blood flow in pan‐colitis is 200 mL/min, which would deliver <italic>N</italic>/5 neutrophils to the colon per min. Therefore, 5/120, or 4%, of incoming neutrophils undergo migration into inflamed bowel. If the 96% of nonmigrating cells exit in a primed state, then at steady state >90% of circulating neutrophils would be primed if no depriming took place. As the highest level of priming seen in IBD is ~40%, this indicates that depriming within the circulation must take place. Using the above values in the steady state equation relating priming rate to depriming rate plus primed‐cell destruction rate gives a mean depriming time of 35 min. We conclude that a very small proportion of neutrophils entering a site of inflammation migrate and that in vivo depriming must take place to limit the numbers of primed neutrophils in the circulation.</p> </abstract>