CANDIDA-ALBICANS STIMULATES CYTOKINE PRODUCTION AND LEUKOCYTE ADHESION MOLECULE EXPRESSION BY ENDOTHELIAL-CELLS

Endothelial cells have the potential to influence significantly the ho st immune response to blood-borne microbial pathogens, such as Candida albicans. We investigated the ability of this organism to stimulate e ndothelial cell responses relevant to host defense in vitro. Infection with C. albicans induced endothelial cells to express mRNAs encoding E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, interleukin 6, interleukin 8, monocyte chemoattractant pro tein 1, and inducible cyclooxygenase (cox2). All three leukocyte adhes ion molecule proteins were expressed on the surfaces of the endothelia l cells after 8 h of exposure to C. albicans. An increase in secretion of all three cytokines was found after 12 h of infection. Cytochalasi n D inhibited accumulation of the endothelial cell cytokine and leukoc yte adhesion molecule mRNAs in response to C. albicans, suggesting tha t endothelial cell phagocytosis of the organism is required to induce this response. Live Candida tropicalis, Candida glabrata, a nongermina ting strain of C. albicans, and killed C. albicans did not stimulate t he expression of any of the cytokine or leukocyte adhesion molecule mR NAs. These findings indicate that a factor associated with live, germi nating C. albicans is required for induction of endothelial cell mRNA expression. Furthermore, since endothelial cells phagocytize killed C. albicans, phagocytosis is likely necessary but not sufficient for thi s organism to stimulate mRNA accumulation. In conclusion, the secretio n of proinflammatory cytokines acid expression of leukocyte adhesion m olecules by endothelial cells in response to C. albicans could enhance the host defense against this organism by contributing to the recruit ment of activated leukocytes to sites of intravascular infection.