Peritoneum

Abstract: IL-17 is a newly discovered cytokine implicated in the regulation of hemopoiesis and inflammation. Because IL-17 production is restricted to activated T lymphocytes, the effects exerted by IL-17 may help one to understand the contribution of T cells to the inflammatory response. We investigated the role of IL-17 in leukocyte recruitment into the peritoneal cavity. Leukocyte infiltration in vivo was assessed in BALB/Cj mice. Effects of IL-17 on chemokine generation in vitro were examined in human peritoneal mesothelial cells (HPMC). Administration of IL-17 i.p. resulted in a selective recruitment of neutrophils into the peritoneum and increased levels of KC chemokine (murine homologue of human growth-related oncogene α (GROα). Pretreatment with anti-KC Ab significantly reduced the IL-17-driven neutrophil accumulation. Primary cultures of HPMC expressed IL-17 receptor mRNA. Exposure of HPMC to IL-17 led to a dose- and time-dependent induction of GROα mRNA and protein. Combination of IL-17 together with TNF-α resulted in an increased stability of GROα mRNA and synergistic release of GROα protein. Anti-IL-17 Ab blocked the effects of IL-17 in vitro and in vivo. IL-17 is capable of selectively recruiting neutrophils into the peritoneal cavity via the release of neutrophil-specific chemokines from the peritoneal mesothelium.

Abstract: Previous studies demonstrate that Ly-1 B cells and their progenitors are clearly detectable in peritoneum in normal mice. In this publication, we show (a) that peritoneal Ly-1 B cells resemble splenic Ly-1 B cells with respect to surface marker expression and functional activity (autoantibody production); (b) that Ly-1 B frequencies in peritoneum are considerably higher than in spleen; and (c) that genetic mechanisms reduce peritoneal Ly-1 B frequencies to minimal levels in SJL-related mice and to below detectability in CBA/N and other mice with the X-linked immunodeficiency (Xid). In addition, we show that that peritoneal (and perhaps splenic) Ly-1 B populations demonstrate an unique bias in immunoglobulin commitment. That is, they are selectively enriched for cells that express IgM heavy chains in association with lambda light chains. Thus, as a whole, evidence presented here defines the peritoneum as a tightly regulated lymphocyte compartment that normally houses a large population of mature Ly-1 B cells with distinctive functional properties.

Abstract: Epithelial mesenchymal transition (EMT), a process involved in many growth and repair functions, has been identified in the peritoneal tissues of patients who undergo peritoneal dialysis. The sequence of changes in gene regulation and cellular events associated with EMT after TGF-beta1-induced peritoneal fibrosis is reported. Sprague-Dawley rats received an intraperitoneal injection of an adenovirus vector that transfers active TGF-beta1 (AdTGF-beta1) or control adenovirus, AdDL. Animals were killed 0 to 21 days after infection. Peritoneal effluent and tissue were analyzed for markers of EMT. In the animals that were treated with AdTGF-beta1, an increase in expression of genes associated with EMT and fibrosis, such as type I collagen A2, alpha-smooth muscle actin, and the zinc finger regulatory protein Snail, was identified. Transition of mesothelial cells 4 to 7 d after infection, with appearance of epithelial cells in the submesothelial zone 7 to 14 d after exposure to AdTGF-beta1, was demonstrated. This phase was associated with disruption of the basement membrane and increased expression of matrix metalloproteinase 2. By 14 to 21 d after infection, there was evidence of restoration of normal submesothelial architecture. These findings suggest that EMT occurs in vivo after TGF-beta1 overexpression in the peritoneum. Cellular changes and gene regulation associated with EMT are evident throughout the fibrogenic process and are not limited to early time points. This further supports the central role of TGF-beta1 in peritoneal fibrosis and provides an important model to study the sequence of events involved in TGF-beta1-induced EMT.

Abstract: To evaluate the role of macrophages in experimental disseminated candidiasis, mouse splenic macrophages were eliminated by i.v. delivery of liposome-entrapped dichloromethylene diphosphonate (L-Cl2MDP). Splenic tissue sections that were immunoperoxidase-stained with mAbs against marginal zone macrophages (MONTS-4), red pulp macrophages (SK39), and neutrophils (SK208) showed that 3 days after L-Cl2MDP treatment, macrophages but not neutrophils were depleted, and circulating neutrophils responded normally to an irritated peritoneum and showed normal phagocytic ability. That is, in response to thioglycollate in the peritoneum, neutrophils migrated in normal numbers to the peritoneal cavity and expressed the normal activation phenotype of high Mac-1 and low Mel-14 Ag levels. These neutrophils also showed normal ability to ingest Candida albicans yeast cells in both in vitro and in vivo assays. However, the spleens from L-Cl2MDP-treated mice lost their ability to bind yeast, which agrees with our previous findings that yeast cells bind specifically to marginal zone macrophages. When macrophage-depleted were systemically challenged with C. albicans, clearance of viable fungal elements from blood was slower, their kidneys had higher recoverable CFU, and both BALB/cByJ and congenitally thymic-deficient (nude) mouse strains did not survive as long as control mice. Mice given L-Cl2MDP recovered most of their macrophage function by 56 days and became normal in their resistance to C. albicans. These results indicate that macrophages play an important role in host resistance to experimental disseminated candidiasis, but the mechanism does not appear to involve T cell functions.