TY - JOUR
T1 - Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions
T2 - Studies in iNOS-deficient mice
AU - Hickey, M. J.
AU - Granger, D. N.
AU - Kubes, P.
PY - 2001/10/20
Y1 - 2001/10/20
N2 - It is well established that constitutive production of nitric oxide is central to numerous processes in the microvasculature, including controlling the trafficking of inflammatory leucocytes. However, during many inflammatory responses induction of inducible nitric oxide synthase (iNOS) increases nitric oxide production. The role of iNOS-derived nitric oxide in modulating leucocyte recruitment is less well understood, although recent studies using iNOS-deficient mice have begun to examine this issue. This article describes much of the work that implicates iNOS as having a role in controlling leucocyte recruitment, including the intravital microscopy studies which revealed that iNOS-deficient mice have elevated leucocyte-endothelial cell interactions during endotoxaemia. Furthermore in additional studies, we compared expression of endothelial adhesion molecules in wild-type and iNOS-deficient mice, under conditions in which iNOS was expressed. Adhesion molecule expression was measured using an in vivo dual radiolabel immunoassay. To induce iNOS, mice were treated with either 1 or 50 μg of bacterial lipopolysaccharide (LPS), and 4 h later expression of P-selectin, E-selectin and vascular cell adhesion molecule-1 was determined in eight different tissues. In nearly all cases, adhesion molecule expression did not differ between the two types of mice, either in the absence of an inflammatory stimulus, or following LPS treatment. These findings indicate that iNOS does not regulate expression of endothelial adhesion molecules either under basal conditions, or during the endotoxaemic response. This further suggests that alterations in leucocyte function may mediate the modulating effect of iNOS on leucocyte recruitment.
AB - It is well established that constitutive production of nitric oxide is central to numerous processes in the microvasculature, including controlling the trafficking of inflammatory leucocytes. However, during many inflammatory responses induction of inducible nitric oxide synthase (iNOS) increases nitric oxide production. The role of iNOS-derived nitric oxide in modulating leucocyte recruitment is less well understood, although recent studies using iNOS-deficient mice have begun to examine this issue. This article describes much of the work that implicates iNOS as having a role in controlling leucocyte recruitment, including the intravital microscopy studies which revealed that iNOS-deficient mice have elevated leucocyte-endothelial cell interactions during endotoxaemia. Furthermore in additional studies, we compared expression of endothelial adhesion molecules in wild-type and iNOS-deficient mice, under conditions in which iNOS was expressed. Adhesion molecule expression was measured using an in vivo dual radiolabel immunoassay. To induce iNOS, mice were treated with either 1 or 50 μg of bacterial lipopolysaccharide (LPS), and 4 h later expression of P-selectin, E-selectin and vascular cell adhesion molecule-1 was determined in eight different tissues. In nearly all cases, adhesion molecule expression did not differ between the two types of mice, either in the absence of an inflammatory stimulus, or following LPS treatment. These findings indicate that iNOS does not regulate expression of endothelial adhesion molecules either under basal conditions, or during the endotoxaemic response. This further suggests that alterations in leucocyte function may mediate the modulating effect of iNOS on leucocyte recruitment.
KW - Adhesion
KW - E-selectin
KW - Inflammation
KW - Nitric oxide
KW - P-selectin
KW - Rolling
KW - Vascular cell adhesion molecule-1
UR - http://www.scopus.com/inward/record.url?scp=0034786383&partnerID=8YFLogxK
U2 - 10.1046/j.1365-201X.2001.00892.x
DO - 10.1046/j.1365-201X.2001.00892.x
M3 - Review Article
C2 - 11678734
AN - SCOPUS:0034786383
SN - 0001-6772
VL - 173
SP - 119
EP - 126
JO - Acta Physiologica Scandinavica
JF - Acta Physiologica Scandinavica
IS - 1
ER -