title: Effect of low doses of lipopolysaccharide prior to ozone exposure on bronchoalveolar lavage: Differences between wild type and surfactant protein A-deficient mice.
abstract: BACKGROUND: Several aspects of the inflammatory response to a single insult, i.e., exposure to 2 ppm of ozone (O(3)) for 3 h or 6 h, are less pronounced in surfactant protein A deficient (SP-A -/-) mice (KO) than in wild type mice (WT). It was hypothesized that a mild insult, specifically low doses of lipopolysaccharide (LPS), would adversely affect host defense and differentially potentiate O(3)-induced injury in WT and KO mice. METHODS: WT and KO mice were treated with different doses of LPS or LPS (2 ng) + O(3) (2 ppm) or filtered air (FA) for 3 h, then sacrificed 4 h following exposure (O(3), FA) or 20 h after LPS treatment alone. Several endpoints of inflammation were measured in bronchoalveolar lavage (BAL). RESULTS: 1) At 20 h after LPS treatment alone, both WT and KO mice exhibited signs of inflammation, but with differences in the macrophage inflammatory protein 2 (MIP-2) response pattern, total cells (at 0.5 ng LPS) and basal levels of oxidized protein and phospholipids; 2) After LPS + O(3), KO compared to WT showed decrease in polymorphonuclear leukocytes (PMNs) and MIP-2 and increase in phospholipids, and after LPS + FA an increase in total cells; 3) WT after LPS + FA showed an increase in SP-A with no further increase after LPS + O(3), and an increase in oxidized SP-A dimer following O(3) or LPS + O(3). CONCLUSIONS: LPS treatment has negative effects on inflammation endpoints in mouse BAL long after exposure and renders KO mice less capable of responding to a second insult. LPS and O(3) affect SP-A, quantitatively and qualitatively, respectively.
authors.affiliation: The Penn State Center for Host defense, Inflammation, and Lung Disease (CHILD) Research, Departments of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033.
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.forename: Todd M
authors.initials: TM
authors.lastname: Umstead
authors.forename: Kwangmi
authors.initials: K
authors.lastname: Ahn
authors.forename: David S
authors.initials: DS
authors.lastname: Phelps
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros