Neutrophils in ulcerative colitis: a review of selected biomarkers and their potential therapeutic implications.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
a Department of Respiratory , Inflammation and Autoimmunity, AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Daniel
D
Muthas
b Department of Cardiovascular and Metabolic Diseases , AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Anna
A
Reznichenko
c Department of Personalised HealthCare & Biomarkers , AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Clare A
CA
Balendran
d Department of Drug Safety and Metabolism , AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Gerhard
G
Böttcher
a Department of Respiratory , Inflammation and Autoimmunity, AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Ib Groth
IG
Clausen
a Department of Respiratory , Inflammation and Autoimmunity, AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Carina
C
Kärrman Mårdh
a Department of Respiratory , Inflammation and Autoimmunity, AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Tomas
T
Ottosson
c Department of Personalised HealthCare & Biomarkers , AstraZeneca R&D Gothenburg , Mölndal , Sweden.
Mohib
M
Uddin
e Blizard Institute, Barts and the London School of Medicine and Dentistry, QMUL , London , UK.
Thomas T
TT
MacDonald
f Department of Gastroenterology , IBD Center, Humanitas Research Hospital , Milan , Italy.
Silvio
S
Danese
a Department of Respiratory , Inflammation and Autoimmunity, AstraZeneca R&D Gothenburg , Mölndal , Sweden.|g Digestive Disease Center K, Bispebjerg Hospital, University of Copenhagen , Copenhagen , Denmark.
Mark
M
Berner Hansen
D015415:Biomarkers / Q000032:analysis*; D002097:C-Reactive Protein / Q000032:analysis; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology*; D005243:Feces / Q000737:chemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D007781:Lactoferrin / Q000032:analysis; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D058990:Molecular Targeted Therapy; D009504:Neutrophils / Q000378:metabolism*
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; D007781:Lactoferrin
Therapy; Ulcerative colitis; biomarkers; clinical development; inflammation; mucosa; neutrophils