Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages

Am J Respir Crit Care Med. 1999 Jun;159(6):1967-74. doi: 10.1164/ajrccm.159.6.9810117.


To determine how resident alveolar macrophages (AM) regulate the antigen-presenting-cell (APC) activities of pulmonary dendritic cells (DC) in the response to particulate antigen, we pretreated Lewis rats intratracheally with liposomes containing clodronate (LIP-CLOD), which eliminated AM in vivo. Controls received saline encapsulated in liposomes (LIP-SAL) or saline alone intratracheally. At Day 3, rats were injected intratracheally with 1 x 10(7) heat-killed Listeria (HKL) and DC purified from lung were examined for their ability to stimulate HKL-immune T cells without added HKL. Only DC from LIP-CLOD-treated rats displayed enhanced APC activities for HKL. A second intratracheal HKL challenge at Day 14 yielded lymphocytic cuffing of the microvasculature in LIP-CLOD-treated lungs only. Intratracheal adoptive transfer of normal syngeneic AM into LIP-CLOD-treated rats suppressed APC activities of DC in vitro and the lymphocytic response in vivo. Bronchoalveolar macrophages from rats treated with LIP-CLOD and HKL showed decreased production of nitric oxide (NO), a potent suppressor of DC and T-helper 1 lymphocyte activities as compared with those of controls. We conclude that eliminating AM in vivo reduces local production of NO and promotes pulmonary cell-mediated immunity to HKL.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / physiology
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / pharmacology
  • Dendritic Cells / immunology
  • Drug Carriers
  • Immunity, Cellular / physiology
  • Liposomes
  • Listeria / immunology*
  • Lung / cytology
  • Lung / immunology*
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / physiology*
  • Macrophages, Alveolar / transplantation
  • Mice
  • Nitric Oxide / metabolism
  • Rats
  • Rats, Inbred Lew


  • Drug Carriers
  • Liposomes
  • Clodronic Acid
  • Nitric Oxide