Remodeling of Peritoneal-like Structures by Mesothelial Cells: Its Role in Peritoneal Healing

Bittinger, Fernando; Schepp, Caroline; Brochhausen, Christoph; Lehr, Hans A.; Otto, Mike; Köhler, Holger; Skarke, Carsten; Walgenbach, S.; Kirkpatrick, Charles James

doi:10.1006/jsre.1998.5449

Cited by 32 publications

(26 citation statements)

References 23 publications

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“…Mesothe- lial cells adjacent to and apposing the wound proliferate giving rise to two populations of cells, those that migrate across the wound surface and those that detach from their substratum, fl oat in the serosal fl uid and settle on the injured surface [29] . Also, it has been proposed that mesothelial cells, possibly originating from undifferentiated mesenchymal cells, move from the underlying connective tissue to the wound surface [30] , although this theory has been disputed by Mutsaers and colleagues [29,31] . Both processes explain the observation that peritoneal wounds heal at the same rate irrespectively of size [32,33] .…”

Section: Discussionmentioning

confidence: 99%

Effect of a Matrix Metalloproteinase Activity and TNF-Alpha Converting Enzyme Inhibitor on Intra-Abdominal Adhesions

et al. 2005

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Background: Formation of intra-abdominal adhesions depends, in part, on the activity of serine proteinases. Matrix metalloproteinases (MMP) are required for epithelialization of skin wounds but their involvement in mesothelialization of peritoneal wounds and in adhesion pathogenesis is not known. Early tumor necrosis factor-α (TNF-α) levels have been proposed to reflect propensity to adhesion formation. Objective: The impact of MMP activity and secreted TNF-α on peritoneal adhesion formation and healing was investigated through systemic administration of the synthetic broad-spectrum MMP and TNF-α-converting enzyme (TACE) inhibitor GM 6001. Methods: Female Sprague-Dawley rats of 4–6 weeks of age were injected subcutaneously daily with GM 6001 100 mg/kg (n = 12) or vehicle (n = 10) starting two days before surgery. In each rat, two standardized peritoneal wounds, 20 mm × 5 mm, were made. One peritoneal wound was sutured whereas the contralateral wound healed by secondary intention. Adhesion formation and peritoneal healing, cell proliferation, and hydroxyproline concentrations were evaluated on postoperative day 7. Results: Total serum TNF-α levels increased in vehicle-treated rats (p = 0.019) while GM 6001 treatment effectively prevented the rise in the postoperative phase (p < 0.001). No significant differences were observed in the extent of adhesion formation (p = 0.67) between control (65.0%) and GM 6001-treated (61.5%) animals, or peritoneal wound healing or cell proliferation. Hydroxyproline levels increased in the wounds (p = 0.014) but were not different between the two groups (p = 0.14). Conclusions: Lack of a striking effect of the MMP and TACE antagonist GM 6001 on postoperative adhesions suggests that MMP activity and TNF-α might not be major adhesiogenic factors.

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Section: Discussionmentioning

confidence: 99%

Effect of a Matrix Metalloproteinase Activity and TNF-Alpha Converting Enzyme Inhibitor on Intra-Abdominal Adhesions

et al. 2005

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“…Mouse peritoneal mesothelial cells (PMCs) were isolated from omental tissue as described previously (19,20). The PMCs (1 ϫ 10 5 cells/well) were plated and cultured on the collagen-coated 24-well dish until they had reached confluence.…”

Section: Chemokine-induced M Aggregation (Cima) Assaymentioning

confidence: 99%

Inhibition of CCL1-CCR8 Interaction Prevents Aggregation of Macrophages and Development of Peritoneal Adhesions

Hoshino¹,

Kawamura²,

Yasuhara

et al. 2007

The Journal of Immunology

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Peritoneal adhesions are a significant complication of surgery and visceral inflammation; however, the mechanism has not been fully elucidated. The aim of this study was to clarify the mechanism of peritoneal adhesions by focusing on the cell trafficking and immune system in the peritoneal cavity. We investigated the specific recruitment of peritoneal macrophages (PMφ) and their expression of chemokine receptors in murine models of postoperative and postinflammatory peritoneal adhesions. PMφ aggregated at the site of injured peritoneum in these murine models of peritoneal adhesions. The chemokine receptor CCR8 was up-regulated in the aggregating PMφ when compared with naive PMφ. The up-regulation of CCR8 was also observed in PMφ, but not in bone marrow-derived Mφ, treated with inflammatory stimulants including bacterial components and cytokines. Importantly, CCL1, the ligand for CCR8, a product of both PMφ and peritoneal mesothelial cells (PMCs) following inflammatory stimulation, was a potent enhancer of CCR8 expression. Cell aggregation involving PMφ and PMCs was induced in vitro in the presence of CCL1. CCL1 also up-regulated mRNA levels of plasminogen activator inhibitor-1 in both PMφ and PMCs. CCR8 gene-deficient mice or mice treated with anti-CCL1-neutralizing Ab exhibited significantly reduced postoperational peritoneal adhesion. Our study now establishes a unique autocrine activation system in PMφ and the mechanism for recruitment of PMφ together with PMCs via CCL1/CCR8, as immune responses of peritoneal cavity, which triggers peritoneal adhesions.

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“…Both inflammatory and neoplastic disease processes involving the abdominal cavity are associated with marked structural alterations of peritoneal mesothelium, which include loss of polarization, cellular retraction with exposure of the submesothelial extracellular matrix (ECM) and frequently detachment and suspension of mesothelial cells in peritoneal effusions [7,27,39]. The precise pathomechanisms involved in the disruption of the mesothelial integrity are still poorly defined but are likely to involve alterations of the expression of mesothelial adhesion molecules [4,6,33].…”

Section: Introductionmentioning

confidence: 99%

Disruption of the integrity of human peritoneal mesothelium by interleukin-1? and tumor necrosis factor-?

et al. 2003

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Inflammatory and neoplastic disease processes of the abdominal cavity are frequently associated with disruption of the integrity of the peritoneal mesothelium. In the present study, we analyzed the effects of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) on the morphology and expression of adhesion molecules of human peritoneal mesothelial cells (HPMC). Treatment of HPMC with IL-1beta and TNF-alpha resulted in a time- and dose-dependent alteration of the normal cobblestone morphology of the mesothelium with loss of polarization, cellular retraction and exposure of the submesothelial matrix. The effect was already observable after 6 h of treatment and was most pronounced at a dose of 10 ng/ml of IL-1beta or TNF-alpha. These morphological alterations were associated with a significant rearrangement of the expression of mesothelial adhesion molecules as detected by flow cytometry. IL-1beta and TNF-alpha both led to a loss of the expression of the hemidesmosomal integrin subunits alpha6 ( P<0.01 and P<0.001) and beta4 ( P<0.01) and an increased expression of the integrin subunit alpha5 ( P<0.001 and P<0.01). IL-1beta furthermore upregulated the expression of the integrin subunits alpha1, alpha2 and the adhesion molecule CD44 while the latter was downregulated by TNF-alpha. Our data indicate that IL-1beta and TNF-alpha may significantly affect disease processes of the abdominal cavity by their potential to disrupt the mesothelial basal cell-matrix adhesion and, thus, the integrity of the peritoneal mesothelial cell lining.

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Remodeling of Peritoneal-like Structures by Mesothelial Cells: Its Role in Peritoneal Healing

Cited by 32 publications

References 23 publications

Effect of a Matrix Metalloproteinase Activity and TNF-Alpha Converting Enzyme Inhibitor on Intra-Abdominal Adhesions

Effect of a Matrix Metalloproteinase Activity and TNF-Alpha Converting Enzyme Inhibitor on Intra-Abdominal Adhesions

Inhibition of CCL1-CCR8 Interaction Prevents Aggregation of Macrophages and Development of Peritoneal Adhesions

Disruption of the integrity of human peritoneal mesothelium by interleukin-1? and tumor necrosis factor-?

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