Phenotypic characterization of alveolar capillary endothelial cells, alveolar epithelial cells and alveolar macrophages in patients with pulmonary fibrosis, with special reference to MHC class II antigens

Komatsu, Takeshi; Yamamoto, Masashi; Shimokata, Kaoru; Nishimura, Hiroshi

doi:10.1007/bf00718607

Cited by 27 publications

(5 citation statements)

References 37 publications

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“…PnIIs express constitutively MHC class II molecules, 18 and this expression is increased by IFN-␥ in rat 23 or in some pathological conditions in human. 40,41 PnIIs also express cathepsins, 42 CD54, 20 and co-stimulatory molecules such as CD80 and CD86. 43 Therefore, these epithelial cells, strategically localized in the lung at the interface with the outside environment, express many of the molecules required for efficient antigen presentation to CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

CD208/Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

Salaun¹,

Saint‐Vis²,

Pacheco

et al. 2004

The American Journal of Pathology

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Dendritic cell-lysosomal associated membrane protein (DC-LAMP)/CD208, a member of the lysosomal associated membrane protein (LAMP) family, is specifically expressed by human DCs on activation. However, its mouse counterpart could not be detected in mature DCs. The present study demonstrates that DC-LAMP is constitutively expressed by mouse, sheep, and human type II pneumocytes. Confocal and immunoelectron microscopy showed that mouse DC-LAMP protein co-localizes with lbm180, a specific marker for the limiting membrane of lamellar bodies that contain surfactant protein B, as well as with intracellular MHC class II molecules that accumulate in the same organelles. Expression of DC-LAMP was also occasionally detected at the cell surface of type II pneumocytes. Interestingly, human bronchioloalveolar carcinoma tumor cells, which correspond to transformed type II pneumocytes, express DC-LAMP. Similar observations were made in the Jaagsiekte sheep retrovirus-associated ovine pulmonary adenocarcinoma, a model of human bronchioloalveolar carcinoma. This study establishes that DC-LAMP is constitutively expressed in normal type II pneumocytes. Furthermore, DC-LAMP appears to be a marker of transformed type II pneumocytes as well, an observation that may help the study and the classifica- The lysosomal associated membrane protein (LAMP) family consists of a group of heavily glycosylated proteins accounting for approximately half of the protein content in the lysosomal membrane. They all contain a conserved intracytoplasmic tyrosine-based lysosome-targeting motif YXX (where represents a bulky hydrophobic residue).1 Several members of this family (LAMP-1 to LAMP-3 and CD68) were cloned in a broad range of species.1 Although LAMP-1 and LAMP-2 are ubiquitously expressed, 2 CD68 is mainly restricted to monocytes and macrophages.3 The latest human LAMP protein identified, DC-LAMP/CD208, was originally described as a molecule specifically expressed in mature dendritic cells (DCs). 4 DC-LAMP appears transiently on DC activation at the limiting membrane of the MHC class II-containing intracellular compartments (MIIC) 4,5 involved in MHC class II peptide loading and transport to the cell surface. 5On further maturation, MHC class II molecules and DC-LAMP segregate: MHC class II molecules are translocated to the cell surface membrane, whereas DC-LAMP concentrates in perinuclear lysosomes. On the basis of these observations, it was proposed that DC-LAMP could play a role in the sorting of the MIIC membrane-associated molecules and the transfer of MHC class II molecules to the cell surface. 4 Human, monkey, and mouse DC-LAMP mRNAs were shown to be expressed in the lung 4,6 -8 but the cellular source was not determined. Of note, murine DC-LAMP was not detected in mouse DCs. 8 In the present study, using specific monoclonal antibodies, we establish that DC-LAMP is specifically expressed by mouse, sheep, and human type II pneumocytes (PnIIs). PnIIs are peripheral pulmonary cells acting as stem cells for repopulation of lung by alve...

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Section: Discussionmentioning

confidence: 99%

CD208/Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

Salaun¹,

Saint‐Vis²,

Pacheco

et al. 2004

The American Journal of Pathology

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“…A number of groups have shown that IFN-␥-treated large vessel endothelial cells cause alloproliferation of resting CD4 ϩ T cells in vitro, allowing them to postulate that constitutively HLA class II-positive endothelial cells cause allostimulation of resting T cells in vivo (4 -6). Similarly, human epithelial cells associated with allografts have been shown to be constitutively positive for HLA-DR in vivo (7)(8)(9)(10) and to up-regulate HLA-DR after IFN-␥ stimulation in vitro (11)(12)(13). However, IFN-␥-stimulated epithelial cells do not induce proliferation of allospecific CD4 ϩ T lymphocytes, and may even induce a state of anergy or nonresponsiveness in vitro (14).…”

mentioning

confidence: 99%

An Epithelial Cell Line That Can Stimulate Alloproliferation of Resting CD4+ T Cells, But Not After IFN-γ Stimulation

McCormack

Moyes

Shi

et al. 2000

The Journal of Immunology

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It has previously been shown that IFN-γ-induced up-regulation of HLA class II on the surface of epithelial cells is not sufficient to induce proliferation of allospecific CD4+ T cells in vitro. To further investigate this phenomenon, a human epithelial bladder carcinoma, T24, was induced to constitutively express HLA class II without IFN-γ stimulation, by permanent transfection with the full-length class II transactivator (CIITA) gene. Proliferation of allospecific T cells to transfected and wild-type cells with and without prior activation with saturating levels of IFN-γ for 4 days was examined. IFN-γ-activated T24 did not induce any response from CD4+ T cells. However, T24.CIITA induced significant levels of alloproliferation, which could be abrogated by pretreatment of T24.CIITA with a mAb to LFA-3. Prestimulation of T24.CIITA with saturating levels of IFN-γ for 4 days also prevented allospecific CD4+ T cell proliferation. These findings suggest that epithelial cells may be intrinsically able to process and present alloantigen and provide adequate costimulation. We propose that IFN-γ has a secondary, as yet unidentified, effect that acts to negatively regulate this response, at least in some epithelial cells.

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“…Then, the indirect HRP-labcled antibody method was applied for immunological re action as previously described [15], Briefly, the procedure involves successive incubations with the first antibodies in optimal dilu tions (rabbit anti-SP antibody 1:600. rabbit anti-CGRP antibody 1:1.200) for 12 It at 4°C, and the second antibody (1:80) for 4 h at 4°C. The antigen-antibody reaction was visualized with 0.25% diaminobenzidinc (DAB) solution containing 0.01 M sodium azide and 0.01 M hydrogen peroxide, and counterstained with methyl green.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Distribution of Substance P-Immunoreactive and Calcitonin Gene-Related Peptide-Immunoreactive Nerves in Normal Human Lungs

Komatsu

Yamamoto

Shimokata

et al. 1991

Int Arch Allergy Immunol

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The distribution of substance P (SP)-immunoreactive (IR) and calcitonin gene-related peptide (CGRP)-IR nerves in normal human lungs was immunohistochemically investigated. SP-IR and CGRP-IR nerves were found in lamina propria and adjacent to blood vessels, and also in some of the ganglia and nerve bundles in the submucosal area. Comparison of serial consecutive sections revealed that SP-IR and CGRP-IR nerves represented similar distribution patterns. CGRP-IR nerves were scarce in bronchial smooth muscles, whereas SP-IR nerves were always present therein. Neither SP-IR nor CGRP-IR nerves were found, however, among submucosal glands or in alveolar septa. These localization patterns were closely related to the functions of SP and CGRP in normal lungs.

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Phenotypic characterization of alveolar capillary endothelial cells, alveolar epithelial cells and alveolar macrophages in patients with pulmonary fibrosis, with special reference to MHC class II antigens

Cited by 27 publications

References 37 publications

CD208/Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

CD208/Dendritic Cell-Lysosomal Associated Membrane Protein Is a Marker of Normal and Transformed Type II Pneumocytes

An Epithelial Cell Line That Can Stimulate Alloproliferation of Resting CD4+ T Cells, But Not After IFN-γ Stimulation

Distribution of Substance P-Immunoreactive and Calcitonin Gene-Related Peptide-Immunoreactive Nerves in Normal Human Lungs

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