Sg. Filler et al., CANDIDA-ALBICANS STIMULATES CYTOKINE PRODUCTION AND LEUKOCYTE ADHESION MOLECULE EXPRESSION BY ENDOTHELIAL-CELLS, Infection and immunity, 64(7), 1996, pp. 2609-2617
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.