Biomedical subjects

Lars Eckmann

Publications and source records attributed to Lars Eckmann.

40 records · Page 3Linked to original sources

PubMed2002

Ubiquitous production of macrophage migration inhibitory factor by human gastric and intestinal epithelium.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) inhibits macrophage migration and has pleiotropic activities on immune and inflammatory responses, cell growth, and glucose metabolism. MIF is produced by T cells, macrophages, and endothelial cells. Because intestinal epithelial cells produce mediators important for regulating mucosal immune and inflammatory responses, we sought to determine if these cells produce MIF. METHODS: MIF expression was determined by immunostaining of human intestinal mucosa, intestinal xenografts, and cultured cells. MIF protein levels were quantitated by enzyme-linked immunosorbent assay and immunoblot analysis, messenger RNA was assessed by real-time reverse-transcription polymerase chain reaction, and functional activity was assessed by enzymatic and migration assays. RESULTS: MIF was abundantly expressed in vivo in gastric, small intestinal, and colonic epithelium and in epithelium lining human intestinal xenografts. MIF was also constitutively expressed at the messenger RNA and protein level by several cultured colon and gastric epithelial cell lines, and its expression in those cells was not up-regulated by the proinflammatory cytokines interleukin 1alpha, tumor necrosis factor alpha, or interferon gamma. Epithelial MIF from cultured cells was released predominantly from the apical side after Salmonella infection, had tautomerase activity, and arrested macrophage migration. CONCLUSIONS: Human intestinal epithelial cells are a major source of MIF, a molecule that can regulate macrophage migration, inflammation, and cell metabolism.

Animals↗

PubMed2002

Small bowel infections.

Infections of the human gastrointestinal tract with enteric pathogens are among the leading causes of disease, suffering, and death worldwide. Enteric pathogens are ingested from contaminated food and water and pass through the entire gastrointestinal tract during establishment in the host and subsequent shedding and spread to new hosts. Nonetheless, each pathogen exploits a unique niche within the intestinal tract and has developed unique strategies to interact with different host cells and functions. The most important and prevalent infections of the small intestine are caused by diarrheagenic Escherichia coli, particularly enterotoxigenic and enteropathogenic E. coli, rotavirus, Giardia lamblia, and Cryptosporidium parvum. This review focuses on recent insights into the pathogenesis of infections with these pathogens and host defenses against them.

Journal Article↗

PubMed2002

Central importance of immunoglobulin A in host defense against Giardia spp.

The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.

Animals↗

PubMed2002

Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium.

Antimicrobial peptides are highly conserved evolutionarily and are thought to play an important role in innate immunity at intestinal mucosal surfaces. To better understand the role of the antimicrobial peptide human cathelicidin LL-37/human cationic antimicrobial protein 18 (hCAP18) in intestinal mucosal defense, we characterized the regulated expression and production of this peptide by human intestinal epithelium. LL-37/hCAP18 is shown to be expressed within epithelial cells located at the surface and upper crypts of normal human colon. Little or no expression was seen within the deeper colon crypts or within epithelial cells of the small intestine. Paralleling its expression in more differentiated epithelial cells in vivo, LL-37/hCAP18 mRNA and protein expression was upregulated in spontaneously differentiating Caco-2 human colon epithelial cells and in HCA-7 human colon epithelial cells treated with the cell differentiation-inducing agent sodium butyrate. LL-37/hCAP18 expression by colon epithelium does not require commensal bacteria, since LL-37/hCAP18 is produced with a similar expression pattern by epithelial cells in human colon xenografts that lack a luminal microflora. LL-37/hCAP18 mRNA was not upregulated in response to tumor necrosis factor alpha, interleukin 1alpha (IL-1alpha), gamma interferon, lipopolysaccharide, or IL-6, nor did the expression patterns and levels of LL-37/hCAP18 in the epithelium of the normal and inflamed colon differ. On the other hand, infection of HCA-7 cells with Salmonella enterica serovar Dublin or enteroinvasive Escherichia coli modestly upregulated LL-37/hCAP18 mRNA expression. We conclude that differentiated human colon epithelium expresses LL-37/hCAP18 as part of its repertoire of innate defense molecules and that the distribution and regulated expression of LL-37/hCAP18 in the colon differs markedly from that of other enteric antimicrobial peptides, such as defensins.

Antimicrobial Cationic Peptides↗