The Regulation of Pulmonary Immunity

Lipscomb, Mary F.; Bice, David E.; Lyons, C. Rick; Schuyler, Mark; Wilkes, David S.

doi:10.1016/s0065-2776(08)60634-3

Cited by 57 publications

(22 citation statements)

References 429 publications

(305 reference statements)

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“…The primary host defense mechanism within the lung during bacterial pneumonia is the rapid clearance of the invading bacteria from the respiratory tract (reviewed in Ref. 4). Although the lung microenvironment contains several distinct leukocyte populations, the first line of defense during pulmonary infection is the alveolar macrophage.…”

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confidence: 99%

γδ-T Cells Are Critical for Survival and Early Proinflammatory Cytokine Gene Expression During MurineKlebsiellaPneumonia

Moore

Newstead

et al. 2000

The Journal of Immunology

145

138

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Although cells of the innate inflammatory response, such as macrophages and neutrophils, have been extensively studied in the arena of Gram-negative bacterial pneumonia, a role for T cells remains unknown. To study the role of specific T cell populations in bacterial pneumonia, mice deleted of their TCR β- and/or δ-chain were intratracheally inoculated with Klebsiella pneumoniae. γδ T cell knockout mice displayed increased mortality at both early and late time points. In contrast, mice specifically lacking only αβ-T cells were no more susceptible than wild-type mice. Pulmonary bacterial clearance in γδ-T cell knockout mice was unimpaired. Interestingly, these mice displayed increased peripheral blood dissemination. Rapid up-regulation of IFN-γ and TNF-α gene expression, critical during bacterial infections, was markedly impaired in lung and liver tissue from γδ-T cell-deficient mice 24 h postinfection. The increased peripheral blood bacterial dissemination correlated with impaired hepatic bacterial clearance following pulmonary infection and increased hepatic injury as measured by plasma aspartate aminotransferase activity. Combined, these data suggest that mice lacking γδ-T cells have an impaired ability to resolve disseminated bacterial infections subsequent to the initial pulmonary infection. These data indicate that γδ-T cells comprise a critical component of the acute inflammatory response toward extracellular Gram-negative bacterial infections and are vital for the early production of the proinflammatory cytokines IFN-γ and TNF-α.

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mentioning

confidence: 99%

γδ-T Cells Are Critical for Survival and Early Proinflammatory Cytokine Gene Expression During MurineKlebsiellaPneumonia

Moore

Newstead

et al. 2000

The Journal of Immunology

145

138

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“…Consistent with this role, lung tissue contains large numbers of memory lymphocytes and lung lymphatics drain into abundant groups of perihilar lymph nodes. 1 The lung is therefore a major "tertiary" lymphoid organ. Perhaps as a result, many lung diseases including asthma, sarcoidosis, and tuberculosis are associated with disordered T cell immunity.…”

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confidence: 99%

Characterisation of adhesion receptors mediating lymphocyte adhesion to bronchial endothelium provides evidence for a distinct lung homing pathway

Ainslie

McNulty²,

Huynh³

et al. 2002

Thorax

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Background:The lung is an important tertiary lymphoid organ and many lung diseases are associated with disordered lung immunity. Unlike the gut (α4β7 binding to MAdCAM-1) and skin (CLA+ve T cells binding to E-selectin) where the adhesion receptors involved in organ specific homing of T cells have been identified, the molecular pathways controlling lymphocyte migration to the lung are unclear. Using a modified version of the Stamper-Woodruff assay we have investigated the receptors mediating adhesion of peripheral blood lymphocytes to airway endothelium. Methods: Longitudinal frozen sections of bronchus (8 µm) obtained from lung resection specimens were incubated with T cell enriched peripheral blood mononuclear cells for 30 minutes under shaking conditions in the presence of a fluorescently labelled polyclonal anti-von Willebrand antibody to identify blood vessels. After fixation the percentage of blood vessels supporting adhesion was measured. Blocking monoclonal antibodies were used to determine the role of individual adhesion receptors in lymphocyte binding. Results: Specific cation dependent binding of lymphocytes to bronchial endothelium was observed which was significantly inhibited by antibodies against P-selectin, PSGL-1, L-selectin, LFA-1, ICAM-1 and ICAM-2 but not E-selectin, VLA-4, VCAM-1 or Mac-1. This was consistent with the pattern of endothelial expression of these receptors with strong expression of P-selectin and ICAM-1, but negligible expression of E-selectin on bronchial endothelium. Conclusion: This study suggests an important role for PSGL-1/P-selectin in T cell migration into the bronchi and provides further evidence for a pattern of recirculation for respiratory tract homing T cells distinct from the gut and skin.

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“…4). The appearance of specific immune cells in pulmonary immune reactions has often been reported (20) and occurred regularly after the influx of innate immune cells. This was again confirmed in the present study.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Effects of a Synthetic 2-Kilodalton Macrophage-Activating Lipopeptide ofMycoplasma fermentansafter Pulmonary Application

Lührmann¹,

Deiters

Skokowa

et al. 2002

Infect Immun

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Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans and animals. Mycoplasma infections are characterized by an influx of neutrophils, followed by an accumulation of macrophages and lymphocytes. The present study deals with the question of which mycoplasmal components cause this host reaction. The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar lavage cells were examined at different times after different doses of 2S-MALP-2. Application of 2.5 g induced a pronounced leukocyte accumulation in the bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2 and 3. Lymphocyte numbers, although amounting to only a few percent of the total bronchoalveolar lavage cells, also increased significantly, with maximal lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count of the lung interstitium was increased on day 3 after treatment. After 10 days all investigated cell populations returned to control levels. Transient chemotactic activity for neutrophils was detected in the bronchoalveolar lavage fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate that mycoplasmal lipoproteins and lipopeptides are probably the most relevant mycoplasmal components for the early host reaction. The primary target cells are likely to be the alveolar macrophages liberating chemokines, which attract further leukocytes.

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The Regulation of Pulmonary Immunity

Cited by 57 publications

References 429 publications

γδ-T Cells Are Critical for Survival and Early Proinflammatory Cytokine Gene Expression During MurineKlebsiellaPneumonia

γδ-T Cells Are Critical for Survival and Early Proinflammatory Cytokine Gene Expression During MurineKlebsiellaPneumonia

Characterisation of adhesion receptors mediating lymphocyte adhesion to bronchial endothelium provides evidence for a distinct lung homing pathway

In Vivo Effects of a Synthetic 2-Kilodalton Macrophage-Activating Lipopeptide ofMycoplasma fermentansafter Pulmonary Application

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