Mj. Hickey et al., Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice, ACT PHYSL S, 173(1), 2001, pp. 119-126
It is well established that constitutive production of nitric oxide is cent
ral to numerous processes in the microvasculature, including controlling th
e trafficking of inflammatory leucocytes. However, during many inflammatory
responses induction of inducible nitric oxide synthase (iNOS) increases ni
tric oxide production. The role of iNOS-derived nitric oxide in modulating
leucocyte recruitment is less well understood, although recent studies usin
g iNOS-deficient mice have begun to examine this issue. This article descri
bes much of the work that implicates iNOS as having a role in controlling l
eucocyte recruitment, including the intravital microscopy studies which rev
ealed that iNOS-deficient mice have elevated leucocyte-endothelial cell int
eractions during endotoxaemia. Furthermore in additional studies, we compar
ed expression of endothelial adhesion molecules in wild-type and iNOS-defic
ient mice, under conditions in which iNOS was expressed. Adhesion molecule
expression was measured using an in vivo dual radiolabel immunoassay. To in
duce iNOS, mice were treated with either 1 or 50 mug of bacterial lipopolys
accharide (LIPS), and 4 h later expression of P-selectin, E-selectin and va
scular cell adhesion molecule-1 was determined in eight different tissues.
In nearly all cases, adhesion molecule expression did not differ between th
e two types of mice, either in the absence of an inflammatory stimulus, or
following LPS treatment. These findings indicate that iNOS does not regulat
e expression of endothelial adhesion molecules either under basal condition
s, or during the endotoxaemic response. This further suggests that alterati
ons in leucocyte function may mediate the modulating effect of iNOS on leuc
ocyte recruitment.