The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury.

Sharma, S. K.; MacLean, James A.; Pinto, Clare; Kradin, Richard L.

doi:10.1164/ajrccm.154.1.8680680

Cited by 91 publications

(81 citation statements)

References 20 publications

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“…46 -48 A role for IFN-␥ in bleomycin-induced interstitial fibrosis is supported by the observations that susceptible versus non-susceptible mouse strains produce high amounts of IFN-␥, 42 depletion of T cells down-regulates both IFN-␥ expression and fibrosis, 35,49 and high levels of IFN-␥ expression and fibrosis are observed in SCID mice, which are susceptible to bleomycin-induced fibrosis. 42 Bleomycin treatment of IFN-␥ knockout mice (IFN-␥ -/-) also resulted in both a significant inhibition of pulmonary inflammation and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Majeski

Paintlia

Lopez

et al. 2003

The American Journal of Pathology

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Bronchiolitis obliterans organizing pneumonia (BOOP) isBronchiolitis obliterans organizing pneumonia (BOOP), first described in 1985, is a pattern of injury characterized histologically as "patchy plugs of fibrous tissue (Masson bodies) filling bronchiolar lumens (bronchiolitis obliterans) and alveolar ducts and spaces (organizing pneumonis)." [1][2][3] This patchy fibrosis may begin as focal lesions within the alveoli and the terminal bronchioles of the lung and progress bilaterally over time. 1 Other histological features include clusters of mononuclear inflammatory cells, chronic inflammation in the walls of the surrounding alveoli with reactive type II cells, increased numbers of foamy macrophages in the alveoli, and preserved lung architecture. 2,4 The development of BOOP is often of unknown etiology (idiopathic BOOP) but BOOP has also been associated as a consequence of lung injury due to environmental toxins, bacterial infections, viral infections, and lung or bone marrow transplantation. 3,5 BOOP is responsive to corticosteroids and treatment with prednisone continues to be the primary treatment for patients with symptomatic and progressive disease. [2][3][4] Since infiltrating lymphocytes are associated with the initiation of BOOP lesions, 6,7 it is possible that these cells play an active role in the progression of inflammatory foci into lesions that are progressively dominated by fibroblasts. In patients with BOOP, there is an increase of activated bronchoalveolar lavage (BAL) lymphocytes with up to 80% to 95% of this cellular infiltrate being comprised of cytotoxic/ suppressor CD8 ϩ T cells. 6 -9 These cells may be involved in the inflammation and subsequent fibrosis occurring in BOOP patients. 2,5,7,10 -12 Several studies have shown that the infiltration of T lymphocytes may be important in the development of other forms of pulmonary fibrosis, although the data from both animal models and patients has been equivocal. [13][14][15][16][17][18] Although these existing models of experimental pulmonary fibrosis have been useful for histopathological and functional investigations of other types of fibrotic events in the lung, the process of fibrotic lesion development in these models may be distinct from BOOP lesion development. Thus, differences in the phenotype of the inflammatory cell infiltrate, expression of soluble mediators, and response to various treatments may be different and,

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Section: Discussionmentioning

confidence: 99%

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Majeski

Paintlia

Lopez

et al. 2003

The American Journal of Pathology

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“…The importance of type 2 cytokine production has been demonstrated in animal models of pulmonary fibrosis (14,17) and in animal models of dermal fibrosis (82). Type 2 cytokine production can lead to pulmonary fibrosis through multiple pathways, including 1) the direct stimulation of extracellular matrix production in fibroblasts by IL-4 (31,32); 2) the indirect stimulation of collagen production by IL-5, through effects on eosinophils (33); 3) the absence of antifibrotic effects of IFN␥ (34); and 4) alternative activation of macrophages, which become profibrotic cells (83).…”

Section: Discussionmentioning

confidence: 99%

“…This network includes, but is not limited to, epithelial cell apoptosis, T cell activation, inflammatory cell influx, latent TGF␤ activation, increased production of type 2 cytokines and monocyte chemotactic protein 1 (MCP-1), reduced prostaglandin E 2 production, an activated coagulation cascade, myofibroblast transformation, and increased extracellular matrix production (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). T cells are essential to the development of pulmonary fibrosis induced by bleomycin, silica, trinitrophenyl hapten, or radiation (13)(14)(15)(16)(17)(18)(19). In all these models of acute lung damage, there is a predominance of early lymphocyte infiltrates in the lungs (13)(14)(15)(16).…”

Section: Group 1 Suggested the Possibility That These T Cells Might Imentioning

confidence: 99%

“…The development of pulmonary fibrosis has been prevented or reduced by depleting T cells with the use of antibodies (14)(15)(16)(17)(18), by blocking T cell costimulation through CD28 (19), and by blocking the Fas/Fas ligand cytolytic effector pathway (13). Connections of activated T cells to the production of type 2 cytokines (14,19) and chemokines (19) and infiltration with macrophages, neutrophils, and eosinophils (13,16,17) have been demonstrated, with reductions in these levels following depletion or blockage of T cells. Some studies, however, have found that an absence or depletion of T cells has no effect on the development of pulmonary fibrosis induced by acute lung damage with bleomycin exposure (20)(21)(22)(23)(24).…”

Section: Group 1 Suggested the Possibility That These T Cells Might Imentioning

confidence: 99%

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Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients

Luzina¹,

Atamas²,

Wise³

et al. 2003

Arthritis & Rheumatism

108

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Objective. Pulmonary fibrosis is a major cause of death in scleroderma patients. Previous studies have shown an increase in CD8؉ T cells in the lungs of scleroderma patients. In the present study, we sought to determine whether activated CD8؉ T cells contribute to pulmonary fibrosis in scleroderma patients through the production and activation of profibrotic mediators.Methods. CD8؉ cells were isolated from bronchoalveolar lavage fluid obtained from 19 scleroderma patients and 7 healthy subjects. The phenotype of these cells was determined using DNA array technology. Expression of selected genes was confirmed in real-time polymerase chain reaction and enzyme-linked immunosorbent assay experiments.

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“…We have chosen to focus on the bleomycin model, as intratracheal instillation of bleomycin into rodents has provided important insights into the molecular pathways leading to fibrotic responses to lung injury (Supplemental Table S1). Limitations of the bleomycin model include the following: 1) the findings in mice are strain dependent, and Haston et al (67) have shown that many of these strain-related differences might be explained by differential expression of bleomycin hydrolase (67,134); 2) the prominent proinflammatory response following bleomycin may not be present in human IPF (115,136,153); and 3) the time course of bleomycin-induced fibrosis is selflimited, whereas human IPF is often an inexorably progressive disease (121).…”

Section: L491mentioning

confidence: 99%

Genetically manipulated mouse models of lung disease: potential and pitfalls

Baron

Choi

Owen

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators.

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The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury.

Cited by 91 publications

References 20 publications

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Respiratory Reovirus 1/L Induction of Intraluminal Fibrosis, a Model of Bronchiolitis Obliterans Organizing Pneumonia, Is Dependent on T Lymphocytes

Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients

Genetically manipulated mouse models of lung disease: potential and pitfalls

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