TY - JOUR
T1 - Neutrophils in ulcerative colitis
T2 - a review of selected biomarkers and their potential therapeutic implications
AU - Muthas, Daniel
AU - Reznichenko, Anna
AU - Balendran, Clare A.
AU - Böttcher, Gerhard
AU - Clausen, Ib Groth
AU - Kärrman Mårdh, Carina
AU - Ottosson, Tomas
AU - Uddin, Mohib
AU - MacDonald, Thomas T.
AU - Danese, Silvio
AU - Berner Hansen, Mark
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Objectives: This review article describes the role of neutrophils in mucosal injury and the resulting crypt abscesses characteristic of ulcerative colitis. We also review selected biomarkers for monitoring neutrophil presence and activity in the mucosa as well as their potential as therapeutic targets. Material: We have collated and selectively reviewed data on the most prominent well-established and emerging neutrophil-related biomarkers and potential therapeutic targets (calprotectin, lactoferrin, CXCR1, CXCR2, MMP-9, NGAL, elafin, HNE, pANCAs, MPO, CD16, CD177, CD64, HNPs, SLPI and PTX3) in ulcerative colitis. Results: Systemic and intestinal neutrophil activity increases substantially in active ulcerative colitis, driving tissue damage and extra-intestinal manifestations. Calprotectin is a robust neutrophil and disease biomarker, and a few neutrophil-related targets are being clinically explored as therapeutic targets. Conclusion: We propose that targeting neutrophils and their inflammatory mediators per se is an opportunity that should be explored to identify new effective medical therapies. The overall clinical goal for neutrophil-targeted therapy will be to modulate, but not completely silence, neutrophil activity, thereby abolishing the destructive inflammation with associated acute and chronic tissue damage without compromising host-defense.
AB - Objectives: This review article describes the role of neutrophils in mucosal injury and the resulting crypt abscesses characteristic of ulcerative colitis. We also review selected biomarkers for monitoring neutrophil presence and activity in the mucosa as well as their potential as therapeutic targets. Material: We have collated and selectively reviewed data on the most prominent well-established and emerging neutrophil-related biomarkers and potential therapeutic targets (calprotectin, lactoferrin, CXCR1, CXCR2, MMP-9, NGAL, elafin, HNE, pANCAs, MPO, CD16, CD177, CD64, HNPs, SLPI and PTX3) in ulcerative colitis. Results: Systemic and intestinal neutrophil activity increases substantially in active ulcerative colitis, driving tissue damage and extra-intestinal manifestations. Calprotectin is a robust neutrophil and disease biomarker, and a few neutrophil-related targets are being clinically explored as therapeutic targets. Conclusion: We propose that targeting neutrophils and their inflammatory mediators per se is an opportunity that should be explored to identify new effective medical therapies. The overall clinical goal for neutrophil-targeted therapy will be to modulate, but not completely silence, neutrophil activity, thereby abolishing the destructive inflammation with associated acute and chronic tissue damage without compromising host-defense.
KW - biomarkers
KW - clinical development
KW - inflammation
KW - mucosa
KW - neutrophils
KW - Therapy
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85008262527&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008262527&partnerID=8YFLogxK
U2 - 10.1080/00365521.2016.1235224
DO - 10.1080/00365521.2016.1235224
M3 - Review article
AN - SCOPUS:85008262527
VL - 52
SP - 125
EP - 135
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
SN - 0036-5521
IS - 2
ER -