Metal Contamination Hotspots at Unregulated Firearm Target Shooting Sites in the Everglades.

Hunters and target shooters can introduce metals into the environment in the form of firearm ammunition, elevating environmental levels of these metals, which may cause plant and animal toxicity. We explored metal accumulation in the Florida Everglades at sites used for firearm target shooting that are unlicensed, unregulated, and not patrolled by law enforcement. We compared concentrations of Pb, Cu, and Al in water and soil among study sites, control sites, and a public shooting range. We also tested plants and invertebrates to identify bioaccumulation or biomagnification. Lead and Cu concentrations in the soil at the target sites were elevated (Pb mean: 11,500.1 µg g; Cu mean: 1558.7 µg g) compared with control sites (Pb mean: 35.3 µg g; Cu mean: 49.3 µg g) and were more similar to the shooting range (Pb mean: 3194.7 µg g; Cu mean: 567.1 µg g). Organisms had elevated Pb and Cu at the target sites, indicating bioaccumulation. For example, Spanish needle [ (L.) DC] had a Pb concentration of 356.9 µg g at one site but averaged 80.3 µg g at the control sites. Grass shrimp () had Pb concentrations averaging 416.1 µg g at target sites but only 18.9 µg g at control sites. Water samples did not have elevated metal levels at the sites. Aluminum levels did not correspond to firearms use. We conclude that the illicit shooting sites are hotspots of metal pollution and pose a risk of contamination to several types of organisms. Because these sites are undocumented and unregulated, remediation may be difficult.

Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis.

Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r(2) = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

Endothelial caveolin-1 regulates pathologic angiogenesis in a mouse model of colitis.

BACKGROUND & AIMS: Increased vascular density has been associated with progression of human inflammatory bowel diseases (IBDs) and animal models of colitis. Pathologic angiogenesis in chronically inflamed tissues is mediated by several factors that are regulated at specialized lipid rafts known as caveolae. Caveolin-1 (Cav-1), the major structural protein of caveolae in endothelial cells, is involved in the regulation of angiogenesis, so we investigated its role in experimental colitis. METHODS: Colitis was induced by administration of dextran sodium sulfate to wild-type and Cav-1(-/-) mice, as well as Cav-1(-/-) mice that overexpress Cav-1 only in the endothelium. Colon tissues were analyzed by histologic analyses. Leukocyte recruitment was analyzed by intravital microscopy; angiogenesis was evaluated by immunohistochemistry and in vivo disk assays. RESULTS: Cav-1 protein levels increased after the induction of colitis in wild-type mice. In Cav-1(-/-) mice or mice given a Cav-1 inhibitory peptide, the colitis histopathology scores, vascular densities, and levels of inflammatory infiltrates decreased significantly compared with controls. Lower levels of leukocyte and platelet rolling and adhesion colitis also were observed in Cav-1(-/-) mice and mice given a Cav-1 inhibitory peptide, compared with controls. Cav-1(-/-) mice that received transplants of wild-type bone marrow had a lower colitis score than wild-type mice. Data from mice that overexpress Cav-1 only in the endothelium indicated that endothelial Cav-1 is the critical regulator of colitis. Genetic deletion or pharmacologic inhibition of endothelial Cav-1 also significantly decreased vascular densities and angiogenesis scores, compared with controls. CONCLUSIONS: Endothelial Cav-1 mediates angiogenesis in experimental colitis. Modulation of Cav-1 could provide a novel therapeutic target for IBD.