Direct evidence of monocyte recruitment to inflammatory bowel disease mucosa.
Alterations in phenotype and function of intestinal macrophages occur in inflammatory bowel disease (IBD) but it is unclear whether these changes result from the recruitment of circulating monocytes to the intestine or from proliferation of resident intestinal macrophages. We sought to demonstrate the arrival of blood monocytes, the precursors of macrophages, in IBD mucosa. Peripheral blood mononuclear cells were isolated from 23 patients with clinically active intestinal inflammation (13 Crohn's disease, eight ulcerative colitis, two infective colitis), then radiolabelled with 99mtechnetium (Tc)-stannous colloid (n = 13) or 111indium (In)-oxine (n = 10) before re-injection and abdominal scanning. Four patients had demonstrable intestinal monocyte uptake using [99mTc]-stannous colloid, while six [111In]-oxine-labelled monocyte scans were positive. Uptake sites correlated with actively inflamed regions. Patients demonstrating monocyte uptake had been treated with corticosteroids for a significantly (P < 0.02) shorter duration (median 3 vs 20 days) than those with negative scans. There was no significant difference between positive and negative scans for disease category, clinical or histological disease, activity, or radioisotope used. Biopsies of inflamed mucosa from two patients suffering ulcerative colitis who had positive scans showed a high proportion of CD14-positive macrophages, 4-9% of which contained autoradiographic grains. These results demonstrate that blood monocytes are recruited to the mucosa of actively inflamed bowel, and suggest that this process may be inhibited by corticosteroids. Moreover, the phenotype of the recently-arrived monocytes indicates their susceptibility to stimulation by lipopolysaccharide, and suggests a mechanism for the continuing inflammation in the bacterial product-rich milieu of IBD.
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
M C
MC
Grimm
W E
WE
Pullman
G M
GM
Bennett
P J
PJ
Sullivan
P
P
Pavli
W F
WF
Doe
D000293:Adolescent; D000328:Adult; D000368:Aged; D001345:Autoradiography; D001706:Biopsy; D002455:Cell Division; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D009942:Organometallic Compounds; D015125:Oxyquinoline / Q000031:analogs & derivatives; D011877:Radionuclide Imaging; D017556:Technetium Compounds; D017971:Tin Compounds
D009942:Organometallic Compounds; D017556:Technetium Compounds; D017971:Tin Compounds; C033493:technetium Tc 99m tin colloid; C032950:indium oxine; D015125:Oxyquinoline