Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages.
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.
Kradin
R L
RL
Departments of Pathology and Medicine, Massachusetts General Hospital, Boston, Massachusetts; and Department of Histology, Amsterdam, The Netherlands. rkradin@partners.org
Liu
H W
HW
van Rooijen
N
N
Springer
K
K
Zhao
L H
LH
Leary
C P
CP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers; D007111:Immunity, Cellular / Q000502:physiology; D008081:Liposomes; D008087:Listeria / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D004337:Drug Carriers; D008081:Liposomes; D004002:Clodronic Acid; D009569:Nitric Oxide