Role of inducible nitric oxide synthase (iNOS) in endotoxin-induced leukocyte recruitment

M. J. Hickey, S. Kanwar, E. G. Sihota, J. D. MacMicking, C. Nathan, J. S. Mudgett, P. Kubes

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Nitric oxide (NO) from exogenous or constitutive sources has anti-adhesive properties, reducing leukocyte/endothelial cell interactions in response to acute inflammatory stimuli. The objective of this study was to determine whether inducible nitric oxide synthase (iNOS) is also capable of inhibiting leukocyte recruitment. Mice received endotoxin (LPS, 30 micrograms/kg, i.v.) and 2-4 hrs later leukocyte rolling and adhesion were examined in postcapillary venules of the cremaster muscle, and sinusoids and postsinusoidal venules of the liver by intravital microscopy. iNOS induction in in wild-type mice was demonstrated by RT-PCR for mRNA and immunohistochemistry. In iNOS-deficient mice, numbers of both rolling and adherent leukocytes were significantly higher than wild-type mice at all time points. Similarly in the hepatic microcirculation, the number of rolling and adherent leukocytes in postsinusoidal venules 3-3.5 hrs after LPS was significantly higher in iNOS-deficient animals compared to wild-type. Leukocyte accumulation in the lung (measured by MPO assay) was also significantly elevated in iNOS-deficient animals. Systemic blood pressure, shear rates, circulating leukocyte numbers and baseline rolling and adhesion did not differ between the two groups of animals. These results suggest that NO released from iNOS is capable of reducing leukocyte accumulation in response to LPS.

Original languageEnglish
JournalThe FASEB Journal
Issue number3
Publication statusPublished - 1 Dec 1997
Externally publishedYes

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