Edema and hemoconcentration in mice experimentally infected with Vibrio vulnificus

Abstract

Vibrio vulnificus (lactose-positive Vibrio), a recently recognized pathogenic marine species, produced extreme hemoconcentration and death within 3 to 6 h after subcutaneous or intraperitoneal injection of 10(8) viable cells into mice; hemotocrit values approached 70% (normal, 45%). About 1 ml of edema fluid accumulated at the site of each subcutaneous injection, and locally increased vascular permeability was demonstrated by a skin bluing assay, using Evans blue dye. A corresponding fluid accumulation did not occur in the peritoneal cavity after an intraperitoneal injection. Filter-sterilized supernatants of cultures grown under a variety of conditions did not produce local edema or lethality, nor did whole Vibrio cells killed by a variety of methods or disrupted by sonic oscillation. Edema fluids collected from infected mice and sterilized by filtration had no effect when they were injected subcutaneously or intraperitoneally into mice. Inocula of 10(9) viable cells of V. vulnificus contained within a diffusion chamber implanted subcutaneously did not produce skin bluing, edema, or lethality; Vibrio cells remained viable and virulent within these chambers for at least 2 weeks. These experiments suggested that vascular permeability changes in V. vulnificus infections may not be attributable to a diffusible toxin and may require direct contact between host cells and viable Vibrio cells.

Role of the Protease in the Permeability Enhancement by Vibrio vulnificus

“…In contrast to our findings showing enhancement of vascular permeability by the killed cells, previous workers who used mouse instead of guinea pig or rat reported that the killed cells had no activity (4). This difference may be attributed to different sensitivity between animal species to cell-associated permeability factor or LPS.…”

“…Extreme hemoconcentration due to edema fluid accumulation and death have been observed experimentally in mice injected with living V. vulnificus cells. (4). Thus, the permeability-enhancing factor which forms edema appears to be important in the pathogenesis of V. vulnificus.…”

Vibrio vulnificus may produce a metalloprotease causing an edematous skin lesion in vivo

“…h Mean * SD of three experiments. the vascular permeability and to form an edematous skin lesion is confirmed to be an important virulence determinant of I/ vulnificus [9,18]. In view of the results obtained in previous [9] and the present study, the following conclusion can be drawn: K vulnificus invading the interstitial-tissue space produce VVP in situ, which induces the generation of chemical mediators, enhancement of vascular permeability, and formation of edematous skin lesion.…”

“…Some investigators have documented no accumulation of the protease into the interstitial-tissue space. For instance, Bowdre et al [18] found that the edematous fluid from infected mice did not enhance the vascular permeability, and that immunization with the filtered edematous fluid did not protect mice from I/. Lulnijkus infection.…”

Enhancement of vascular permeability due to histamine-releasing effect of Vibrio vulnificus protease in rat skin

“…In the latter group, cutaneous lesions, such as builae, erythema or necrotic ulcer, often appear on one or more extremities. Bowdre et al [3] and Poole and Oliver [4] reported that living V. vulnifio~s cells injected subcutaneously into mice produced gross edema and that the mice died due to extreme hemoconcentration. Therefore, the permeability-enhancing or edemaforming factor or factors seem important in the pathogenesis of the vibrio.…”