Bactericidal/permeability-increasing protein in colonic mucosa in ulcerative colitis.

BACKGROUND/AIMS: Increased mucosal concentration of bactericidal/permeability-increasing protein (BPI) has been shown in inflammatory bowel diseases. The purpose of the present study was to investigate the relationship between the mucosal concentration of BPI and the grade of mucosal inflammation in ulcerative colitis. METHODOLOGY: Samples of colonic mucosa from 12 patients with ulcerative colitis and from 8 control patients were studied. The concentration of BPI in tissue extracts was measured by a time-resolved fluoroimmunoassay. The concentration of BPI was compared between samples with histological inflammatory changes of different severity. BPI was localized in tissue sections by immunohistochemistry. RESULTS: The concentration of BPI was higher (p < 0.001) in samples of colonic mucosa from patients with ulcerative colitis (median: 3.2 micrograms/g, range: 0.3-22.6 micrograms/g) than in control samples (0.4 microgram/g, 0.1-0.6 microgram/g,). Moreover, the concentration of BPI was higher (p = 0.015) in samples with severe inflammation (2.5 mu/g, 0.3-22.6 micrograms/g) than in those with mild inflammation (0.5 mu/g, 0.3-2.5 micrograms/g). The concentration of BPI in mucosal samples correlated well with the degree of histological inflammation (Spearman R = 0.70, p = 0.01). BPI was localized in polymorphonuclear leukocytes in the mucosa and stroma of the colonic wall. CONCLUSIONS: The concentration of BPI is increased in the colonic mucosa of patients with ulcerative colitis. The increase in the concentration of BPI in colonic mucosa seems to be closely associated with the inflammatory activity of ulcerative colitis.

Time-resolved fluoroimmunoassay for bactericidal/permeability-increasing protein.

Bactericidal/permeability-increasing protein (BPI) is a cationic antimicrobial protein produced by polymorphonuclear leukocytes, that specifically interacts with and kills Gram-negative bacteria. BPl competes with lipopolysaccharide-binding protein (LBP) secreted by liver cells into blood plasma for binding to lipopolysaccharide (LPS) and thus reduces the proinflammatory effects of LPS. We have developed a time-resolved fluoroimmunoassay for BPI and measured the concentration of BPI in human serum and plasma samples. The assay is based on a rabbit antibody against recombinant BPI. This antibody specifically adheres to polymorphonuclear leukocytes in immunostained human tissues. The difference in the serum concentration of BPI between unselected hospitalized patients with and without an infection was statistically significant. The mean concentration of BPI in serum samples was 28.3 mug/l (range 1.64-132, S.D. 26.8, n = 83). In contrast, there was no difference between the two groups in the BPI levels in plasma samples. For all individuals tested, BPI levels were consistently higher in plasma samples compared to the matched serum samples. The mean concentration of BPI in plasma samples was 52.3 mug/l (range 0.9-403, S.D. 60.6, n = 90). There was a positive correlation between the concentration of BPI and the white blood cell count as well as between the BPI concentration and C-reactive protein (CRP) in serum samples. In conclusion, the present study demonstrates that BPI can be quantified reliably by time-resolved fluoroimmunoassay in human serum samples.