ABSTRACT
Cultured murine macrophages (RAW 264.7) were used to evaluate the temporal relationships between cytotoxicity, phagocytosis, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production, and alterations in expression of stress proteins after exposure to cadmium oxide (CdO) or cadmium chloride (CdCl(2)), particulate and soluble forms of cadmium, respectively. Macrophages were exposed in vitro to CdO (25 or 50 microg) or CdCl(2) (30 or 40 microM) for 2 to 72 h. Cytotoxicity was not evident until 18 h when exposed to 30 microM CdCl(2) or 25 microg CdO, but occurred as early as 12 h after exposure to 40 microM CdCl(2) or 50 microg CdO. Relative to untreated controls, phagocytic activity decreased progressively from 2 to 24 h after exposure to both forms of cadmium. TNF-alpha levels increased to 2- to 3-fold after 4 h and remained elevated until 24 h after exposure to 25 and 50 microg CdO and 30 microM CdCl(2), but decreased by 18-24 h at 40 microM CdCl(2). CdCl(2) or CdO alone did not induce NO; however, both cadmium species reduced lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner. Enhanced de novo synthesis of 70- and 90-kD heat shock, or stress, proteins was observed 2 to 8 h after exposure to both CdCl(2) and CdO; however, synthesis of these proteins returned to control levels by 24 h. Stress protein synthesis was enhanced by CdCl(2) or CdO prior to cytotoxicity, but coincided with a decrease in phagocytic capacity and an increase in TNF-a levels. The data suggest that cultured macrophages respond similarly in vitro to a particulate form and a soluble form of cadmium in a cell type that plays a pivotal role in inflammatory and immune responses.
Subject(s)
Cadmium Chloride/pharmacology , Cadmium Compounds/pharmacology , Macrophage Activation/drug effects , Macrophages, Peritoneal/drug effects , Oxides/pharmacology , Animals , Cadmium Chloride/chemistry , Cadmium Compounds/chemistry , Cell Line/drug effects , Cytotoxicity, Immunologic/drug effects , Drug Evaluation, Preclinical , Gene Expression Regulation/drug effects , HSP70 Heat-Shock Proteins/biosynthesis , HSP70 Heat-Shock Proteins/genetics , HSP90 Heat-Shock Proteins/biosynthesis , HSP90 Heat-Shock Proteins/genetics , Inflammation , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/physiology , Mice , Nitric Oxide/biosynthesis , Oxides/chemistry , Particle Size , Phagocytosis/drug effects , Solubility , Suspensions , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/geneticsABSTRACT
This study was undertaken to evaluate the risk of infection (defined as the recovery of the relevant organism from the implant site) in a mouse model when low numbers of bacteria were present on an implanted biomaterial. Segments of different types of suture with adherent bacteria were implanted subcutaneously into mice. The infection risk with Staphylococcus aureus was greater than with Staphylococcus epidermidis RP62A or Candida albicans. The infection risk with the implantation of multifilament sutures was significantly greater than with monofilament sutures. When <10 colony forming units (cfu) of S. aureus were present on monofilament suture material, the infection rate was 3%. When <10 cfu of S. aureus were present on multifilament suture material, the infection rate was 7%. An infection rate of 15% occurred with <10 cfu of S. aureus on multifilament nylon sutures. When >10 but <20 cfu of S. aureus were present, the infection rates were 4 and 51%, respectively. These data confirm that the infection rate with multifilament sutures (or porous materials) is greater than with monofilament sutures (or solid materials) when the organisms are encountered at implantation (acute model) and indicate that a significant risk of infection may occur when only a few organisms are on a device at implantation.
