Results from the present studies show that adhesion molecules were
expressed in ocular tissues after intravitreal injection of viable
S. aureus. Adhesion molecule expression precedes leukocyte
entry, as published in our previous model.
24 Our in vivo
experiments showed that E-selectin expression peaked at 6 to 24 hours
in
S. aureus–injected eyes, slowly declined, and returned
to constitutive levels at 72 hours. The rapid and sustained expression
of E-selectin in the iris, CB, and retinal vessels is similar to the in
vivo findings of Suzuma et al.
42 in a rat model of
endotoxin-induced uveitis. In this model, E-selectin expression was not
detected in the iris, CB, or retina 5 hours after LPS injection but was
detectable in these structures after 7 hours. Expression remained
present in these tissues for 24 hours. Our findings also are comparable
with other in vivo reports in which E-selectin expression was
detectable on microvessels up to 72 hours after LPS injection in
cutaneous models of inflammation.
43 The time course of
E-selectin expression seen in our model is similar to that seen in in
vitro studies of microvascular endothelial cells
44 45 but
not large-vessel endothelial cells in which E-selectin is rapidly
induced and rapidly decreased.
46 In vitro studies have
demonstrated that dermal microvascular endothelial cells show a peak
E-selectin expression at 6 to 8 hours and sustained expression after
treatment with TNF.
44 In contrast to E-selectin, in vitro
ICAM-1 expression peaks between 16 to 24 hours and persists at peak
levels as long as proinflammatory cytokines are present.
47 Our in vivo ICAM-1 data are consistent with these findings.
Upregulation of ICAM-1 expression was first seen at 6 hours, with
maximal expression occurring at 24 hours followed by decreases in
staining intensities at 48 and 72 hours. The sustained in vivo
expression pattern of E-selectin and ICAM-1 seen in our model may be in
response to vitreous bacterial products and/or cytokines whose
production we have shown to be increased after injection of viable
S. aureus.
25 In the present study, the 24-hour
peak in ICAM-1 expression corresponded to the peak levels of
intravitreal TNF-α, IL-1β, cytokine-induced neutrophil
chemoattractant (CINC), and interferon-γ.