Absence of circulating aldosterone attenuates foreign body reaction around surgical sutures.

BACKGROUND AND AIMS: Adrenal hormones influence inflammatory and fibrotic activity and thereby are involved in wound-healing process. Any excess as well as any shortage of glucocorticoids leads to a delayed wound healing. Mineralocorticoids like aldosterone have a pro-fibrotic and pro-inflammatory impact; thus, reduction of circulating aldosterone should result in an attenuated inflammatory response to implanted foreign bodies. MATERIAL AND METHODS: Eighteen rats were bilaterally adrenalectomized and substituted with dexamethasone (12 microg/kg per day) and 1% salt in their drinking water; 22 rats were sham-operated. The surgical suture material was removed after 3 weeks and analyzed for size of granuloma, ratio of collagen type I/III, apoptotic cells (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling), expression of matrix metalloproteinase (MMP)-2, cyclooxygenase 2, tumor necrosis factor receptor 2 (TNF-R2), cluster of differentiation 68 (CD68), Ki67, and cold shock protein Y box binding protein 1 (YB-1). Cell expression was scored according to Remmele. RESULTS: All animals developed foreign body granulomas around the sutures. Absence of circulating aldosterone after adrenalectomy (ADX) was associated with smaller granuloma size and a reduced ratio of collagen type I/III. Ki67 and MMP-2 showed the strongest expression in cells of the infiltrate around suture. In adrenalectomized rats, we observed significantly less CD68-positive macrophages and less Ki67-positive cells but no significant differences in the expression of YB-1, TNF-R2, or MMP-2. Looking for correlations and co-expressions of proteins, the number of significant Spearman correlations was reduced in the ADX group compared to controls (one and four, respectively). CONCLUSION: The absence of circulating aldosterone attenuates inflammatory intensity around suture material. Foreign body granuloma seems to be an appropriate model to study chronic inflammatory process.

Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene expression by macrophages and fibroblasts.

Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that orchestrates tissue remodeling. In the present study the spatial and temporal distribution of MMP-2 gene transcription, protein synthesis, and enzymatic activity were analyzed following polymeric mesh (polyglactin, polypropylene) implantation in transgenic reporter mice harboring MMP-2 regulatory sequences -1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages within the foreign body granuloma via sequences -1686/+423 with concomitantly up-regulated protein synthesis and enzymatic activity. Macrophages distant from mesh filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh material displayed strong MMP-2 gene transcription independent of the included promoter sequences, whereas fibroblasts without close contact to mesh material had low MMP-2 synthesis rates due to silencing activity of sequences -1686/-1241. In vitro studies support a cellular crosstalk concept, as macrophages trans-repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk in foreign body reaction that may provide a new approach for mesh modification.