Lipopolysaccharide-induced cell cycle arrest in macrophages occurs independently of nitric oxide synthase II induction

Biochim Biophys Acta. 2001 May 28;1539(1-2):140-6. doi: 10.1016/s0167-4889(01)00102-1.


Lipopolysaccharide (LPS, a Gram-negative bacterium cell wall component) is a potent macrophage activator that inhibits macrophage proliferation and stimulates production of nitric oxide (NO) via NO synthase II (NOSII). We investigated whether NO mediates the LPS-stimulated cell cycle arrest in mouse bone marrow-derived macrophages (BMM). The addition of the NO donor DETA NONOate (200 microM) inhibited BMM proliferation by approx. 80%. However, despite NO being an antimitogen, LPS was as potent at inhibiting proliferation in BMM derived from NOSII-/- mice as from wild-type mice. Consistent with these findings, LPS-induced cell cycle arrest in normal BMM was not reversed by the addition of the NOSII inhibitor S-methylisothiourea. Moreover, in both normal and NOSII-/- BMM, LPS inhibited the expression of cyclin D1, a protein that is essential for proliferation in many cell types. Despite inhibiting proliferation DETA NONOate had no effect on cyclin D1 expression. Our data indicate that while both LPS and NO inhibit BMM proliferation, LPS inhibition of BMM proliferation can occur independently of NOSII induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cells, Cultured
  • Cyclin D1 / analysis
  • Isothiuronium / analogs & derivatives
  • Isothiuronium / pharmacology
  • Lipopolysaccharides*
  • Macrophage Activation
  • Macrophage Colony-Stimulating Factor
  • Macrophages / drug effects*
  • Mice
  • Mice, Knockout
  • Nitric Oxide Donors
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / deficiency*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Nitrites / analysis


  • Lipopolysaccharides
  • Nitric Oxide Donors
  • Nitrites
  • Cyclin D1
  • Isothiuronium
  • Macrophage Colony-Stimulating Factor
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • S-methylisothiopseudouronium