Role of Intercellular Adhesion Molecule 1 in Acute Lung Injury Induced by Candidemia

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.

Intercellular adhesion molecule 1-dependent activation of interleukin 8 expression in Candida albicans-infected human gingival epithelial cells

“…Although anti-ICAM-1 antibody is known to inhibit T-cell adhesion and immune function (31), it seems that the anti-ICAM-1 MAb used in this study did not modify the activation of HGECs but inhibited the direct binding of C. albicans with HGECs. Our result supported a previous report that ICAM-1 plays a role in the adherence of C. albicans to pulmonary vascular endothelial cells (34). In both studies, however, inhibition of C. albicans adhesion to host cells by anti-ICAM-1 antibody was not complete.…”

Lung Diseases - Selected State of the Art Reviews

“…Expression of these adhesion molecules is induced by the production of pro-inflammatory cytokines such as TNF- and IL-1 (Osborn et al, 1989;Masinovsky et al, 1990), which have been reported as important inflammatory components in a variety of lung diseases including those caused by fungi (Hamacher & Schaberg, 1994;Izzo et al, 1998;Yokomura et al, 2001;Yu & Limper, 1997). In our PCM mouse model, we have observed that lungs of mice infected intranasally with P.brasiliensis conidia show a higher expression of adhesion molecules during the first 4 days post-challenge.…”

Candida albicans -Endothelial Cell Interactions: a Key Step in the Pathogenesis of Systemic Candidiasis

“…Of these molecules, only ICAM-1 and -2 are widely expressed on endothelial cells, although CD14 was recently identified on primary, but not passaged, cultures of human umbilical vein endothelial cells (49). There are no data on the role of CD14, CD102, or CD242 as a possible endothelial ligand for C. albicans adhesion, but Yokomura et al (82) have shown that anti-CD54 monoclonal antibodies can partially inhibit the adhesion of yeast forms of C. albicans to rat pulmonary artery endothelial cells in vitro and significantly prolong the survival of rats injected intravenously with C. albicans. In certain circumstances, it is also possible that ␣ M ␤ 2 ligands such as fibrinogen, heparin and iC3b could in turn bind to endothelial cells and act as an intermediary in Candida-endothelial cell adhesion.…”