Transcriptional and functional profiling defines human small intestinal macrophage subsets

Macrophages (Mfs) are instrumental in maintaining immune homeostasis in the intestine, yet studies on the origin and heterogeneity of human intestinal Mfs are scarce. Here, we identified four distinct Mf subpopulations in human small intestine (SI). Assessment of their turnover in duodenal transplants revealed that all Mf subsets were completely replaced over time; Mf1 and Mf2, phenotypically similar to peripheral blood monocytes (PBMos), were largely replaced within 3 wk, whereas two subsets with features of mature Mfs, Mf3 and Mf4, exhibited significantly slower replacement. Mf3 and Mf4 localized differently in SI; Mf3 formed a dense network in mucosal lamina propria, whereas Mf4 was enriched in submucosa. Transcriptional analysis showed that all Mf subsets were markedly distinct from PBMos and dendritic cells. Compared with PBMos, Mf subpopulations showed reduced responsiveness to proinflammatory stimuli but were proficient at endocytosis of particulate and soluble material. These data provide a comprehensive analysis of human SI Mf population and suggest a precursor-progeny relationship with PBMos.

Equine Colitis X Associated with Infection by Clostridium Difficile NAP1/027

A 14-year-old Quarter Horse with a 48-hr history of colic was euthanized after failure to respond to treatment. At necropsy, cecal and colonic mucosae were congested throughout, and there was segmental edema and significant thickening of the intestinal wall. Excessive numbers of mononuclear cells were found in mucosal lamina propria. Submucosal hemorrhage was diffuse and extensive, and Clostridium difficile toxins A and B were detected. Large numbers of C. difficile were isolated, and genetic characterization revealed them to be North American pulsed-field gel electrophoresis type 1, polymerase chain reaction ribotype 027, and toxinotype III. Genes for the binary toxin were present, and toxin negative–regulator tcdC contained an 18-bp deletion. This genotype comprises the current human “epidemic strain,” which is associated with human C. difficile–associated disease of greater than historical severity. The diagnosis was peracute typhlocolitis, with lesions and history typical of those attributed to colitis X.

Uremic Gastropathy in the Dog

Stomachs of four dogs with uremia and four normal dogs were examined. Uremic stomachs represented four types of disease: atrophic, amyloidotic, ulcerative and necrotic gastropathy. Pathologic changes common to all uremic stomachs were expansion of the lamina propria, atrophy of gastric glands, and submucosal arteriopathy; lesions were limited to body and fundic zones. Lamina propria was markedly expanded by edema, mastocytosis, deposition of acidic mucosubstances, fibroplasia and mineralization. Capillaries in lamina propria had swollen endothelium and calcium salts were present extracellularly as amorphous granular laminae. Gastric glands were distorted and irregular and had fewer cells per unit of tissue. Parietal cells were swollen and had fragmentation of cytocavitary network and mitochondrial swelling with calcification. Chief cells were shrunken, agranular and atrophic with foci of glycogen and dilation of endoplasmic reticulum. Argentaffin cell content was diminished. Muscular arteries of submucosae had segmental degenerative lesions characterized by myocyte necrosis, calcification, and deposition of acidic mucosubstances and fibrin; thrombosis and obstructive arteriopathy were common. These studies suggest that uremic gastropathy is a disease of mucosal lamina propria and that lesions were due to anoxia caused by diffuse vascular injury and to altered parietal cell function.

EFFECTS OF HEPARIN AND ASBESTOS WITH CORTICOTROPHIN ON THE MUCOSAL MAST CELLS AND TISSUE EOSINOPHILS OF RAT STOMACH

ABSTRACT Intact rats were injected once with a suspension of asbestos and for 5 days with 2 IU of adrenocorticotrophin-zinc per day. 1.0 mg of heparin was injected intraperitoneally 9 times at 12-hourly intervals and the same amount of ACTH intramuscularly. The rats were decapitated 5 days after the injection of asbestos, 24 hours after the last ACTH injection and 3 hours after the last heparin injection. The mucosal mast cells and tissue eosinophils of the stomach were counted from the body mucosa and recorded per mm2 of tissue. Heparin caused no changes in either the mast cell count or tissue eosinophilia, nor did it bring about any changes in the degranulation of mucosal mast cells during the ACTH effect, or in the destruction of tissue eosinophilia. Asbestos peritonitis seemed to have a degranulating effect on mucosal mast cells and a destructive effect on tissue eosinophilia. It also appeared to increase the effect of ACTH on the mucosal cells. It is suggested that glucocorticoids stimulated by ACTH exert such an immediate effect on the function of the cells of the mucosal lamina propria that the inhibitory effect of heparin and asbestos is counteracted.