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

Lipopolysaccharide (LPS, a Gram-negative bacterium cell wall component) is a potent macrophage activator that inhibits macrophage proliferation and st imulates production of nitric oxide (NO) via NO synthase II (NOSII). We inv estigated whether NO mediates the LPS-stimulated cell cycle arrest in mouse bone marrow-derived macrophages (BMM). The addition of the NO donor DETA N ONOate (200 muM) inhibited BMM proliferation by approx. 80%. However, despi te NO being an antimitogen, LPS was as potent at inhibiting proliferation i n BMM derived from NOSII-/- mice as from wild-type mice. Consistent with th ese findings. LPS-induced cell cycle arrest in normal BMM was not reversed by the addition of the NOSII inhibitor S-methylisothiourea. Moreover, in bo th normal and NOSII-/- BMM, LPS inhibited the expression of cyclin D1, a pr otein that is essential for proliferation in many cell types. Despite inhib iting proliferation DETA NONOate had no effect on cyclin D1 expression. Our data indicate that while both LPS and NO inhibit BMM proliferation, LPS in hibition of BMM proliferation can occur independently of NOSII induction. ( C) 2001 Elsevier Science B.V. All rights reserved.