BackgroundUlcerative colitis, an inflammatory bowel disease, is associated with the massive infiltration of neutrophils. Although the initial infiltration of neutrophils is beneficial for killing bacteria, it is presumed that persistent infiltration causes tissue damage by releasing antibacterial products as well as inflammatory cytokines. A murine C-type lectin receptor, dendritic cell immunoreceptor 1 (Dcir1), is expressed on CD11b+ myeloid cells, such as macrophages, dendritic cells and neutrophils. It was reported that Dcir1 is required to maintain homeostasis of the immune system to prevent autoimmunity, but it is also involved in the development of infectious disease resulting in the enhanced severity of cerebral malaria. However, the role of Dcir1 in intestinal immune responses during colitis remains unclear. In this study, we investigated the role of Dcir1 in intestinal inflammation using an experimental colitis model induced with dextran sodium sulfate (DSS).ResultsIn contrast to wild type (WT) mice, Dcir1−/− mice exhibited mild body weight loss during the course of DSS colitis accompanied by reduced colonic inflammation. Dcir1 deficiency caused a reduced accumulation of neutrophils in the inflamed colon on day 5 of DSS colitis compared with WT mice. Consistently, the production of a neutrophil-attracting chemokine, MIP-2, was also decreased in the Dcir1−/− colon compared with the WT colon on day 5. There were fewer myeloperoxidase-positive neutrophils in the inflamed colon of Dcir1−/− mice than in that of WT mice. Moreover, bone marrow neutrophils from Dcir1−/− mice produced less reactive oxygen species (ROS) by lipopolysaccharide stimulation than those from WT mice. This suggests that Dcir1 deficiency decreases the accumulation of tissue destructive neutrophils during DSS colitis.ConclusionDcir1 enhances the pathogenesis of DSS colitis by altering neutrophil recruitment and their functions.

A 70-year-old man was referred to our hospital on June 25, 1999 because of recurrent painful tonic spasms in the upper abdomenand lower extremities. The patient used to work as a carpenter and had been retired for several years. He also had worked as a coal miner for a brief period. An appendectomy was performed at the age of 20. He underwent parathyroidectomy because of hyperparathyroidism in 1993. An episode of gout occurred some years before admission. He had been given diagnoses of hyperuricemia, essential hypertension, and supraventricular arrhythmia someyears earlier, and had been treated elsewhere. The treatment had been discontinued for morethan half a year at presentation.On physical examination, a tophus-like nodule was palpated in the right auricle. The patient's liver, spleen, and lymph nodes were not palpated. There was slight tenderness in the epigastrium. Neurological examination was negative. The temperature was 35.7°C, the blood pressure was 154/90 mmHg,and the pulse was 84/min and irregular.AnECGrevealed supraventricular and ventricular premature contractions. An abdominal computed tomographic (CT) scan disclosed a small simple cyst in the left lateral lobe of the liver (Fig. 1A). Upper gastrointestinal endoscopic and total colonoscopic examinations were performed because of positive tests for occult blood of feces. The patient had mild gastritis and colonic adenomatouspolyps. Cranial CT scan disclosed two lacunar infarctions in the bilateral basal ganglia. Since electroencephalogram disclosed abnormalspikes, sodium valpronate was begun under a tentative diagnosis of symptomatic epilepsy with modest improvement of the tonic spasms. Laboratory data on admission disclosed abnormal liver function tests (aspartate aminotransferase 121 IU//, alanine aminotransferase 68 IU//, and alkaline phosphatase 364 IU//), that returned spontaneously to the normal levels. Since the serum uric acid level was high (9.3 mg/dl), benzbromarone was prescribed. The serum uric acid level rapidly returned to the nor- antibiotics developed in a 70-year-old man suffering from intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill-defined hypodensity mass on computedtomographic scan and wasenhanced on dynamicmagnetic resonance imaging. The tumor was surgically removed and a diagnosis of IPT was made. Fever and arthritis resolved completely after surgery. Possible interaction between IPT of the liver and gouty arthritis was suggested. (Internal Medicine 40: 493-498, 2001)

Upon injection of D-galactosamine and lipopolysaccharide, Dcir1 -/-mice showed decreased mortality rates and serum levels of alanine aminotransferase (ALT). In early onset hepatitis, serum levels of TNF-α, which primarily cause inflammation and hepatocyte apoptosis, were significantly lower in Dcir1 -/-mice than in wild type (WT) mice. In the liver of Dcir1 -/-mice, influx of neutrophils and other leukocytes decreased.Consistently, the levels of neutrophil-chemoattractant chemokine CXCL1/KC, but not CXCL2/MIP-2, were lower in Dcir1 -/-mice than in WT mice. However, chemotaxis of Ishiguro and Fukawa et.al.3