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.

[1]  D. Christiani,et al.  Expression of inducible nitric oxide synthase by macrophages in rat lung. , 1997, American journal of respiratory and critical care medicine.

[2]  R. Kradin,et al.  Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity. , 1996, The American journal of pathology.

[3]  P. Holt,et al.  Cytokine modulation of the immunosuppressive phenotype of pulmonary alveolar macrophage populations. , 1995, Immunology.

[4]  R. Kradin,et al.  The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen , 1995, The Journal of experimental medicine.

[5]  N. Van Rooijen,et al.  Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. , 1994, Journal of immunological methods.

[6]  R. Simmons,et al.  Reactive nitrogen intermediates suppress the primary immunologic response to Listeria. , 1993, Journal of immunology.

[7]  E. Schneeberger,et al.  FcR+/- subsets of Ia+ pulmonary dendritic cells in the rat display differences in their abilities to provide accessory co-stimulation for naive (OX-22+) and sensitized (OX-22-) T cells. , 1993, The American journal of pathology.

[8]  P. Holt,et al.  Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages , 1993, The Journal of experimental medicine.

[9]  P. Holt,et al.  Regulation of antigen-presenting cell function(s) in lung and airway tissues. , 1993, The European respiratory journal.

[10]  P. Holt,et al.  Regulation of immune response to inhaled antigen by alveolar macrophages: differential effects of in vivo alveolar macrophage elimination on the induction of tolerance vs. immunity , 1991, European journal of immunology.

[11]  E. Schneeberger,et al.  Accessory cells of the lung. II. Ia+ pulmonary dendritic cells display cell surface antigen heterogeneity. , 1991, American journal of respiratory cell and molecular biology.

[12]  E. Schneeberger,et al.  Accessory cells of the lung. I. Interferon-gamma increases Ia+ dendritic cells in the lung without augmenting their accessory activities. , 1991, American journal of respiratory cell and molecular biology.

[13]  N. Van Rooijen,et al.  Alveolar macrophage elimination in vivo is associated with an increase in pulmonary immune response in mice , 1989, The Journal of experimental medicine.

[14]  P. Holt,et al.  Functional studies on macrophage populations in the airways and the lung wall of SPF mice in the steady-state and during respiratory virus infection. , 1988, Immunology.

[15]  C. Nathan,et al.  Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. , 1988, Journal of immunology.

[16]  C. Rochester,et al.  Dendritic cells from rat lung are potent accessory cells. , 1988, The American review of respiratory disease.

[17]  P. Holt.  Down-regulation of immune responses in the lower respiratory tract: the role of alveolar macrophages. , 1986, Clinical and experimental immunology.

[18]  Jon,et al.  ACCESSORY AND STIMULATING PROPERTIES DENDRITIC CELLS AND MACROPHAGES ISOLATED FROM VARIOUS RAT TISSUES* OF BY WOLFGANG , 1982 .

[19]  J. Butler,et al.  The local and systemic IgA and IgG antibody responses of rabbits to a soluble inhaled antigen: measurement of responses in a model of acute hypersensitivity pneumonitis. , 1982, The American review of respiratory disease.

[20]  C. Henney,et al.  Cell-Mediated Immunity Shown by Lymphocytes from the Respiratory Tract , 1970, Science.

[21]  P. Holt,et al.  Alveolar macrophages from humans and rodents selectively inhibit T-cell proliferation but permit T-cell activation and cytokine secretion. , 1995, Immunology.

[22]  Lyons Cr.  The Role of Nitric Oxide in Inflammation , 1995 .

[23]  P. Holt,et al.  Dendritic cells in the respiratory tract. , 1990, International reviews of immunology.

[24]  S. Ahlstedt,et al.  Immune responses in rats sensitized with aerosolized antigen. Antibody formation, lymphoblastic responses and mast cell and mucous cell development related to bronchial reactivity. , 1983, International archives of allergy and applied immunology.