Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis.
OBJECTIVE
Accumulation and infiltration by neutrophil granulocytes is a prominent feature in the local inflammatory process in ulcerative colitis (UC). The present study was performed to evaluate human neutrophil lipocalin (HNL) as a specific neutrophil marker in the inflamed lesions of the colon and rectum in patients with colitis and proctitis.


METHODS
The activity of intestinal neutrophils with respect to release of granule proteins was studied in 18 patients with UC (10 with colitis and eight with isolated proctitis) and in 18 healthy controls using perfusion fluid and biopsies from the sigmoid colon and rectum. The released amounts of the neutrophil granule proteins HNL and myeloperoxidase (MPO) were determined by radioimmunoassays, and the location of HNL and MPO in biopsies from colonic mucosa was examined by immunohistochemistry.


RESULTS
Mucosal release of HNL and MPO was increased 10-55-fold in patients with colitis and proctitis compared with controls. Their bowel biopsies demonstrated that only neutrophils were stained with anti-HNL. We also found correlations between HNL and levels of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8) in perfusion fluids from the sigmoidal segments of patients with proctitis, between HNL and GM-CSF in rectal segments in patients with proctitis, and in sigmoidal segments in patients with colitis.


CONCLUSIONS
We conclude that the increased release of HNL and MPO in colorectal perfusion fluids indicates neutrophil involvement in the local inflammatory process, and suggest that HNL may serve as a specific marker of intestinal neutrophil activation in UC. GM-CSF, and to some extent IL-8, may play a role in neutrophil accumulation and priming in this disease.
Carlson
M
M
Laboratory for Inflammation Research, Department of Medical Sciences, University of Uppsala, Sweden. marie.carlson@medsci.uu.se
Raab
Y
Y
Sevéus
L
L
Xu
S
S
Hällgren
R
R
Venge
P
P
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D007413:Intestinal Mucosa; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*; D015513:Oncogene Proteins; D009195:Peroxidase / Q000378:metabolism; D011349:Proctitis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase