Constitutively produced nitric oxide released by endothelial cells has been
shown to act as an endogenous agent which inhibits the rolling and adhesio
n of leucocytes in the microcirculation. However, during various types of i
nflammation, expression of the inducible form of nitric oxide synthase (iNO
S) can dramatically increase the amount of nitric oxide present in tissues.
Furthermore, as iNOS can be expressed by a wide variety of cell types, the
distribution of nitric oxide is likely to be altered relative to that in u
nstimulated tissue. Under these conditions, it is less well understood whet
her iNOS-derived nitric oxide retains the anti-adhesive capabilities of con
stitutively produced nitric oxide. This review summarizes work done to exam
ine this issue. Three main approaches have been used. In vitro studies have
examined the role of iNOS in adhesive interactions between stimulated endo
thelial cells and leucocytes, providing evidence of an anti-adhesive effect
of iNOS. In addition, the role of iNOS has been examined in vivo in animal
models of inflammation using pharmacological iNOS inhibitors. These experi
ments were extended by the advent of the iNOS-deficient (iNOS(-/-)) mouse.
Intravital microscopy studies of these mice have indicated that, under cond
itions of low-dose endotoxaemia, iNOS-derived nitric oxide can inhibit leuc
ocyte rolling and adhesion. The potential mechanisms for these effects are
discussed. In contrast, several other stud ies have observed either no effe
ct or an enhancing effect of iNOS on inflammatory leucocyte recruitment. Ta
ken together, these studies suggest that the importance of iNOS in modulati
ng leucocyte recruitment can vary according to the type of inflammatory res
ponse.