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Role of intercellular adhesion molecule 1 in acute lung injury induced by candidemia
I Yokomura1, Y Iwasaki, K Nagata
1Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan. iycyay@ec.mbn.or.jp
Abstract:
Candidemia, a complication often affecting immunocompromised patients, is a common cause of acute lung injury. Yeast-phase Candida albicans has been shown to express a protein that is antigenically and structurally related to Mac-1. C. albicans is reported to stimulate intercellular adhesion molecule 1 (ICAM-1) expression on endothelial cells. In this study, the authors examined the role of ICAM-1 in acute lung injury induced by candidemia. The authors cultured rat pulmonary artery endothelial cells (RPAEC) and investigated the effect of anti-ICAM-1 antibodies on adhesion of C. albicans to RPAEC. In addition, the authors administered anti-ICAM-1 antibodies to rats to examine the effect of the antibodies on experimentally induced candidemia. Survival rates, lung wet-to-dry (W/D) weight ratios, bronchoalveolar lavage (BAL) fluid, histopathological findings, and colony-forming units (CFUs) of lung C. albicans were examined. The adherence of C. albicans to RPAEC was significantly decreased by anti-ICAM-1 antibodies. Anti-ICAM-1 antibodies significantly increased survival, decreased lung W/D weight ratios, decreased neutrophil counts in the BAL fluid, reduced microscopic lung injury, and decreased the quantity of lung C. albicans. These results indicate that ICAM-1 plays a role in adherence of C. albicans to pulmonary vascular endothelial cells, which likely leads to invasion of lung tissue by the organism.
Insights
Intercellular Adhesion Molecule 1 (ICAM-1) contributes to Candida albicans adherence in the lungs, worsening acute lung injury. Blocking ICAM-1 with antibodies improved survival and reduced lung damage in candidemia models.
Area of Science:
- Immunology
- Pathology
- Microbiology
Background:
- Candidemia, a fungal infection, is a frequent cause of acute lung injury, particularly in immunocompromised individuals.
- Yeast-phase Candida albicans expresses a protein similar to Mac-1 and stimulates intercellular adhesion molecule 1 (ICAM-1) on endothelial cells.
Purpose of the Study:
- To investigate the role of ICAM-1 in acute lung injury caused by candidemia.
- To evaluate the therapeutic potential of anti-ICAM-1 antibodies in a candidemia model.
Main Methods:
- Cultured rat pulmonary artery endothelial cells (RPAEC) to assess Candida albicans adhesion.
- Administered anti-ICAM-1 antibodies to rats with experimentally induced candidemia.
- Measured survival rates, lung injury markers (wet-to-dry weight ratio, BAL fluid analysis, histopathology), and fungal burden (CFUs).
Main Results:
- Anti-ICAM-1 antibodies significantly reduced Candida albicans adherence to RPAEC.
- Antibody treatment led to increased survival rates in rats.
- Lung injury markers, including neutrophil infiltration and fungal load, were significantly decreased following anti-ICAM-1 antibody administration.
Conclusions:
- ICAM-1 plays a critical role in the adherence of Candida albicans to pulmonary vascular endothelial cells.
- Targeting ICAM-1 with antibodies represents a potential therapeutic strategy to mitigate acute lung injury during candidemia.