PMID- 8579128 OWN - NLM STAT- MEDLINE DCOM- 19960311 LR - 20181113 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 148 IP - 2 DP - 1996 Feb TI - Sequestration of inhaled particulate antigens by lung phagocytes. A mechanism for the effective inhibition of pulmonary cell-mediated immunity. PG - 657-66 AB - Dendritic cells (DCs) have emerged as the dominant antigen-presenting cells (APCs) of the lung, playing a vital role in the induction of cell-mediated immunity to inhaled antigens. We have previously demonstrated that an airway challenge with the soluble antigen hen egg lysozyme yields rapid acquisition of specific antigen-presenting cell activity by purified pulmonary DCs and a cell-mediated immune response in the lung upon secondary challenge. To examine how a particulate antigen leads to a cell-mediated response in vivo, graded concentrations of heat-killed Listeria (HKL) were injected intratracheally into Lewis rats. The bacteria were rapidly ingested by lung macrophages and polymorphonuclear leukocytes. The ability of purified pulmonary DCs pulsed in vivo by an airway challenge with HKL to subsequently stimulate HKL-specific responses ex vivo showed a threshold response, requiring a dose in excess of 10(9) organisms/rat. By contrast, all dosages of HKL yielded specific sensitization of lymphocytes in the draining bilar nodes. Pulmonary DCs purified from rats after a secondary in vivo airway challenge with HKL at day 14 were ineffective antigen-presenting cells except at high dosages of antigen. The generation of cell-mediated pulmonary inflammation paralleled the antigen-presenting cell activity of pulmonary DCs and was observed only at high antigen dosages. Hen egg lysozyme immobilized onto polystyrene beads and injected intratracheally yielded comparable results to those observed with HKL. We suggest that a pulmonary cellular immune response is generated to an inhaled particulate antigen when the protective phagocytic capacities of the lung are exceeded and antigen is able to interact directly with interstitial DCs. The diversion of particulate antigens by pulmonary phagocytes may help to limit undesirable pulmonary inflammation while allowing the generation of antigen-specific immune lymphocytes in vivo. FAU - MacLean, J A AU - MacLean JA AD - Department of Pathology, Massachusetts General Hospital, Boston 02114, USA. FAU - Xia, W AU - Xia W FAU - Pinto, C E AU - Pinto CE FAU - Zhao, L AU - Zhao L FAU - Liu, H W AU - Liu HW FAU - Kradin, R L AU - Kradin RL LA - eng GR - AI01245/AI/NIAID NIH HHS/United States GR - HL48385/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens, Bacterial) RN - EC 3.2.1.17 (Muramidase) SB - IM MH - Animals MH - Antigens, Bacterial/*immunology MH - Bronchoalveolar Lavage Fluid/immunology MH - Dendritic Cells/*immunology MH - Female MH - Immunity, Cellular MH - Inflammation/immunology MH - Listeria monocytogenes/immunology MH - Lung/*immunology MH - Macrophages, Alveolar/*immunology MH - Muramidase/immunology MH - Neutrophils/*immunology MH - Phagocytes/immunology/*pathology MH - *Phagocytosis MH - Rats MH - Rats, Inbred Lew MH - T-Lymphocytes/immunology PMC - PMC1861667 EDAT- 1996/02/01 00:00 MHDA- 1996/02/01 00:01 PMCR- 1996/08/01 CRDT- 1996/02/01 00:00 PHST- 1996/02/01 00:00 [pubmed] PHST- 1996/02/01 00:01 [medline] PHST- 1996/02/01 00:00 [entrez] PHST- 1996/08/01 00:00 [pmc-release] PST - ppublish SO - Am J Pathol. 1996 Feb;148(2):657-66.