Low incidence of bronchus-associated lymphoid tissue (BALT) in chronically inflamed human lungs

The relevance of bronchus-associated lymphoid tissue (BALT) in man is still under discussion. Animal experiments indicate that the development of BALT is dependent on microbial stimulation. Therefore, the incidence of BALT was investigated retrospectively in specimens removed during surgical procedures on patients with chronic pulmonary inflammation. All these patients had severe chronic bronchitis and bronchiectasis, but BALT was found in only 8%. In patients with BALT and a malignant tumor, occlusion of a bronchus with poststenotic pneumonia was always present and BALT was observed exclusively in areas peripheral to the occlusion. In man other compartments of the lung must be responsible for the immune function of BALT found in animals. Partly presented at the Congress of the Eur. Respir. Soc, 21.- 26.9.1991 in Brussels. (Abstract: Eur Respir J. 4, Suppl. 14:217p)     

Low incidence of bronchus-associated lymphoid tissue (BALT) in chronically inflamed human lungs.

The relevance of bronchus-associated lymphoid tissue (BALT) in man is still under discussion. Animal experiments indicate that the development of BALT is dependent on microbial stimulation. Therefore, the incidence of BALT was investigated retrospectively in specimens removed during surgical procedures on patients with chronic pulmonary inflammation. All these patients had severe chronic bronchitis and bronchiectasis, but BALT was found in only 8%. In patients with BALT and a malignant tumor, occlusion of a bronchus with poststenotic pneumonia was always present and BALT was observed exclusively in areas peripheral to the occlusion. In man other compartments of the lung must be responsible for the immune function of BALT found in animals.     

Ovalbumin-induced immunomorphologic reaction of rat lung with emphasis on bronchus-associated lymphoid tissue (BALT)

Specific pathogen-free albino rats exposed to a series of 5 intratracheal inoculations of pure ovalbumin presented hyperplasia of main bronchi BALT-aggregates, the lymph and plasma cells infiltrated with immunofluorescent elements extending up to the distal end of the bronchial tree. The most intensely reactive alterations, particularly of perivascular proliferations rich in antibody-containing cells were observed in intramuscularly stimulated rats with ovalbumin emulsified in complete Freund's adjuvant. The lung structures of animals subcutaneously stimulated with ovalbumin solution were similar to those of controls.     

The specificity of the high endothelial venule in bronchus-associated lymphoid tissue (BALT)

By using an in vitro binding assay, the specificity of T and B cell adherence on high endothelial venules (HEV) of bronchus-associated lymphoid tissue (BALT) was studied in the rat and the guinea pig. It was found that the adherence specificity of the BALT HEV is different from that found in Peyer's patches and more closely resembles the specificity of the HEV in mesenteric lymph nodes. The data are discussed in view of a common mucosal immune system.     

Vimentin antibodies stain membranous epithelial cells in the rabbit bronchus-associated lymphoid tissue (BALT)

Summary The lymphoepithelium covering the bronchus-associated lymphoid tissue (BALT) of the rabbit lung was studied with monoclonal antibodies against vimentin, using the indirect immunoperoxidase technique. In the lymphoepithelium single cells which had a membranous apical cytoplasm and engulfed intraepithelial lymphocytes were vimentin-immunoreactive. All other epithelial cells of the lymphoepithelium and of the surrounding airway epithelium did not bind vimentin antibodies. The results support the hypothesis that the membranous epithelial cells in the lymphoepithelium of rabbit BALT are analogous with intestinal M-cells, which in rabbit Peyer's patches and appendix are selectively labelled by vimentin antibodies.     

Postnatal development of bronchus-associated lymphoid tissue (BALT) in the rat, Rattus norvegicus.

The pattern of development of bronchus-associated lymphoid tissue (BALT) in specified-pathogen-free and conventional (non-barrier maintained) rats over the initial 4 weeks of life appeared to be similar. BALT first appeared around the 2nd week of life and increased in amount over the following 2 weeks. Overlying large nodules of BALT the bronchial epithelium becomes infiltrated by lymphocytes to form a lymphoepithelium. This transformation occurs earlier in conventional rats, possibly because of the differing antigen levels to which they are exposed.     

Specific antibody-forming cells in bronchus-associated lymphoid tissue (BALT) and lung of the rat after intratracheal challenge with horseradish peroxidase

After intratracheal or subcutaneous priming with horseradish peroxidase (HRP), no anti-HRP-forming cells were present in the bronchus-associated lymphoid tissue (BALT) or the lung of the rat. After intratracheal priming and intratracheal boosting with HRP no specific antibody-forming cells were observed either in the BALT or the lung. A few blast cells containing anti-HRP antibody were found in paratracheal lymph nodes, which is possibly the source of anti-HRP-forming cells. After subcutaneous priming in the hind footpad and intratracheal boosting specific antibody-forming cells were present in both the BALT and in the lung. In the BALT these cells were found peripherally, and in the lung perivascularly and peribronchiolarly. The simultaneous appearance of these anti-HRP-forming cells at both sites, their localization and their morphology strongly indicate that they are recruited from the circulation and not formed in situ; the probable source is the popliteal lymph node.     

Vimentin antibodies stain membranous epithelial cells in the rabbit bronchus-associated lymphoid tissue (BALT).

The lymphoepithelium covering the bronchus-associated lymphoid tissue (BALT) of the rabbit lung was studied with monoclonal antibodies against vimentin, using the indirect immunoperoxidase technique. In the lymphoepithelium single cells which had a membranous apical cytoplasm and engulfed intraepithelial lymphocytes were vimentin-immunoreactive. All other epithelial cells of the lymphoepithelium and of the surrounding airway epithelium did not bind vimentin antibodies. The results support the hypothesis that the membranous epithelial cells in the lymphoepithelium of rabbit BALT are analogous with intestinal M-cells, which in rabbit Peyer's patches and appendix are selectively labelled by vimentin antibodies.     

Lymphocyte subpopulations in high endothelial venules and lymphatic capillaries of bronchus-associated lymphoid tissue (BALT) in the rat

The subpopulations of lymphocytes and non-lymphoid cells in high endothelial venules (HEV) and in lymphatic capillaries surrounding lymphoid follicles in bronchus-associated lymphoid tissue (BALT) were examined by electron microscopy after preembedding the tissue and staining with an immunoperoxidase technique. The results were compared with those obtained in gut-associated lymphoid tissue (GALT) reported previously. Monoclonal mouse-anti-rat T cell, IgG, IgM, IgA, and Ia antisera were used. Plasma cells that were reactive to anti-IgG, anti-IgM, and anti-IgA were detected as cells in which the 3',3'-diaminobenzidine tetrahydroxychloride reaction product was localized in rough endoplasmic reticulum and perinuclear spaces but not on plasma membranes. These plasma cells did not occur in either lymphatic capillaries or HEV in BALT as they did in GALT. Cells with surface Ig (sIg cells), T-cell antigen (T cells), and Ia antigen (Ia cells) were present in BALT. T cells were located predominantly in the follicular area opposite the bronchial epithelium; IgM- and IgG-reactive cells were found in the follicular area adjacent to the bronchial epithelium; and IgA-positive cells were found in the lateral part of the area where the T cells were localized (T-cell area). Ia cells were abundant throughout BALT and in moderate numbers in the epithelium. A striking observation was the presence of "nurse-cell"-like structures in the periphery of BALT. The percentages of T, sIgG, sIgM, and sIgA cells in the HEV were 54.7%, 2.4%, 28.9%, and 27.3%, respectively, and in the lymphatic capillaries, 41.2%, 3.8%, 38.2%, and 21.2%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

A morphologic study of bronchus-associated lymphoid tissue in turkeys

Bronchus-associated lymphoid tissue (BALT) in normal turkeys of ages 1 day and 1, 2, 3, 4, 8, and 18 weeks was examined by light microscopy and by scanning and transmission electron microscopy. Turkey BALT resembled other mucosa-associated lymphoid tissues; it was made up of a population of lymphocytes covered by a specialized epithelium different from typical pseudostratified ciliated columnar bronchial epithelium. There were distinct age-related differences in BALT structure. Bronchus-associated lymphoid nodules were larger and more numerous in older turkeys. In 1-day- to 2-week-old turkeys, the primary cell type of BALT epithelium was nonciliated cuboidal; in 2-week old turkeys it was squamous; and in turkeys older than 4-weeks of age, the epithelium was primarily ciliated columnar. In 1- to 4-week old turkeys, large numbers of intraepithelial lymphocytes disrupted the normal organization of the epithelium. In older turkeys, epithelial and lymphoid cells were in discrete compartments separated by connective tissue. Lymphocytes in 1-day-old turkeys were found in loose aggregates around venules and within the epithelium. In 1-week old turkeys, lymphocytes were organized into compartments of morphologically similar cells. By 3-weeks of age, lymphocytes were present in distinct germinal centers. Epithelial cells of BALT did not have large numbers of apical vesicles and thus were not structurally specialized for antigen uptake by endocytosis. However, the epithelial barrier appeared to be disrupted over lymphoid nodules, suggesting that antigen would be readily available to lymphocytes and phagocytes in BALT. Age-related differences in turkey BALT structure may have functional consequences with respect to the respiratory immune response.     

Bronchus-associated lymphoid tissue (BALT) in the laboratory-bred and wild rat, Rattus norvegicus.

In juvenile wild rats, bronchus-associated lymphoid tissue (BALT) development was similar to that seen in adult specified-pathogen-free rats. In adult wild rats the BALT was widespread. In one animal infected with a mycoplasma-like organism, a region of bronchoepithelium overlying a large BALT nodule was seen, through which lymphocytes appeared able to pass to make direct contact with the bronchial lumen: the significance of this observation is discussed. There was no evidence of infection in lungs from any of the specified-pathogen-free animals, where small foci of BALT were seen.     

Non-lymphoid cells of bronchus-associated lymphoid tissue of the rat in situ and in suspension

Immunohistochemical, enzyme-histochemical and electron-microscopical methods were used to study non-lymphoid cells of control and stimulated rat bronchus associated lymphoid tissue (BALT) in situ and in suspensions. Particular attention was paid to the so-called antigen-handling cells, i.e., the interdigitating cells (IDC), which are situated in the T-cell areas, the follicular dendritic cells (FDC), which appear to be restricted to germinal centers, and macrophages, present both in T-cell and B-cell areas. The interdigitating cells were distinguished by being Ia-positive and by the presence of acid phosphatase and non-specific esterase activity in an area near the nucleus. Follicular dendritic cells could be observed in situ by using a monoclonal antibody and by the in vitro trapping of HRP-anti-HRP complexes. Several types of macrophages were found. At the electron-microscopical level no well-developed IDC and FDC could be detected in control BALT. However, in BALT of lipopolysaccharide-stimulated and mycoplasma-infected rats, well-developed IDC and FDC were found. It can be concluded that IDC's and FDC's can be found in BALT.     

Cell-cell and cell-matrix adhesion molecules in human heart and lung transplants

The interaction of immune cells with endothelial and target cells and extracellular matrix in human organ transplants is regulated by a number of receptor-ligand molecules. The molecules mediating intercellular adhesion and activation are classified as integrin, immunoglobulin and selectin families. In the present study the patterns of their cellular expression in human heart and lung transplants are described in normal state and during transplant rejection. The results reveal an organ specific regulation of the different adhesion molecules during transplant rejection. Specific differences were noted in the endothelial expression of vascular ligand molecules in the vascular segments of heart and lung transplants, especially in the lung capillaries. Cell type specific patterns of intercellular and cell-matrix adhesion molecules as their ligands were found in different states of graft rejection. Intravascular and interstitial differences in the expression patterns of leukocyte adhesion receptors support a concept of their stepwise function during graft infiltration. The implications for the organ specific appearance of inflammatory reactions in human heart and lung transplants as for immunosuppressive therapy are discussed.     

Bronchial-associated lymphoid tissue (BALT) response to airway challenge with cigarette smoke, bovine antigen and anti-pulmonary serum.

The bronchial-associated lymphoid tissue (BALT) is a lymphoepithelial organ, related to the immune defence of the lung and to alveolar clearance, which changes size in certain states of disease. Changes in the size of BALT were quantified and compared, and Spearman's test was used to test the relation with the bronchial epithelium. A total of 180 rats were used, divided into 6 groups of 30 as follows: 1) untreated controls; 2) exposed to cigarette smoke for two months; 3) treated with anti-pulmonary serum three doses daily over five days; 4) exposed to cigarette smoke and treated with anti-pulmonary serum; 5) sensitized with bovine albumin and exposed to an environment containing this antigen for two months; 6) exposed to cigarette smoke and bovine albumin. The lungs were processed for histological study, and were stained with the PAS-Alcian blue method. The main left bronchi BALT was studied, and the following were quantified: Lymphatic area (LA), as a percentage of the lung surface occupied by BALT; the flat epithelium (FEp), as the length of bronchial epithelium anatomically related to LA, whose cells tend to adopt a flat shape; the Contact epithelium (Cep), as the length of bronchial epithelium which is in direct contact with the LA. A percentage count of bronchial cells was made in the following classifications: globet cells; globet cells stained with the PAS-Alcian blue method; flat cells; lymphoepithelium cells; columnar cells; and bronchial epithelium cells excluding the above two cell types.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal epithelium and mediation of lymphoid cell adherence

The epithelium of the human oviduct expresses the major histocompatibility complex (MHC) class II and shows endocytic properties towards luminal antigens. Therefore, the epithelial cells might behave as antigen-presenting cells, inducing a local immune response. The activation of antigen-specific T cells not only requires presentation of the peptide antigen by MHC class II, but also the presence of co-stimulatory molecules in the antigen-presenting cells. Therefore, the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1 expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR assay, and the expression was restricted to the luminal border of ciliated and secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide treatments increased the percentage of ICAM-1-positive cells in primary cultures, indicating that the expression of ICAM-1 in the oviduct might be upregulated in vivo by inflammatory cytokines or bacterial infections. Binding assays between allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte adherence. The presence of ICAM-1, in addition to MHC class II, supports the putative role of the oviductal epithelium in antigen presentation. The exclusive apical distribution of ICAM-1 indicates that T-cell activation would occur in a polarized manner. Binding of lymphoid cells to the surface of the oviductal epithelium may help to retain these immune cells that are required for the clearance of pathogens.     

Expression of adhesion molecules and mucins in human and rhesus macaque gastrointestinal epithelial cells

Epithelial junctions and mucins play key roles in the gastrointestinal mucosal barrier, and their alterations are associated with numerous diseases, including carcinomas. The systematic expression of adhesion molecules and mucins in normal and malignant human gastrointestinal cells was investigated in this study. In normal human gastrointestinal cells, zonula occludens-1 (ZO-1), α-catenin, β-catenin, γ-catenin and desmoglein-2 (DSG2) were located in the cytoplasmic membranes, whereas symplekin stained in the nuclei. ZO-1, the three catenins, and DSG2 were observed in the gastric and colorectal carcinomas with reduced and heterogeneous expression and with abnormal distribution. Symplekin was detected in the nuclei of tumor cells in most tumors but not observed in some others. The immunohistochemical results for ZO-1 and symplekin on the tissues were consistent with the data for the cultured cells obtained by immunocytochemical staining and Western blot analysis. MUC1 was not stained in the normal gastrointestinal cells without periodate oxidation, but it was strongly labeled in the malignant gastrointestinal cells. MUC2 was detected in the normal and malignant gastrointestinal cells without the periodate treatment. These findings indicate that alterations in the expression of the epithelial junctions and mucins are associated with the malignant transformation of gastrointestinal cells. In addition, the gastrointestinal epithelial cells of rhesus macaques expressed these adhesion molecules and mucins, as did the human cells, suggesting that the rhesus monkey is a suitable experimental animal model for research on adhesion molecules and mucins.     

Expression of inducible cell adhesion molecules in the normal human lung: immunohistochemical study of their distribution in pulmonary blood vessels

 The distribution of cell adhesion molecules in the normal human lung was investigated using antibodies to E-selectin, P-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Lectin staining by Ulex europaeus type I agglutinin (UEA I) and immunohistochemistry for von Willebrand factor (vWF) was used to visualize a maximum of blood vessels per section. In the bronchial mucosa, staining for P-selectin was positive in ca 90%, and staining for E-selectin, VCAM-1, and ICAM-1 was positive in 40–70% of the vessels stained with UEA I. In the pulmonary circulation (vasa publica) ca 90% of non-capillary vessels stained by anti-vWF expressed P-selectin, 54% VCAM-1, 41% E-selectin, and only ca 20% ICAM 1. The alveolar capillaries were stained consistently by UEA I, but not by the panel of antibodies tested. The alveolar epithelium and, inconstantly, basal cells of the bronchial epithelium were positive for ICAM-1. The distribution pattern of inducible adhesion molecules in normal human lung tissue suggests that a permanent low-grade endothelial activation may exist in particular in the mucosa of the airways, which could be due to the normal antigen exposure via inhaled air. Accepted: 28 April 1998     

Changes occurring in the epithelium covering the bronchus-associated lymphoid tissue of rats after intratracheal challenge with horseradish peroxidase

Summary Changes occurring in the epithelium covering bronchus-associated lymphoid tissue (BALT) in the rat after several intratracheal administrations of horseradish peroxidase (HRP) were studied using morphological and ultrastructural methods. The epithelium is invaded by W3/ 25-positive (T-helper) lymphocytes, the BALT epithelial cells become Ia-positive and develop microvilli; there is an apparent loss of cilia. The number of non-ciliated cells in stimulated BALT increases. The non-ciliated cells can be subdivided into two cell types, one with electron-dense cytoplasm and cytoplasmic granules and the other without granules. The electron-density of the latter cell type is intermediate between that of the ciliated cells and that of the granulecontaining non-ciliated cells. The granule-containing cell types may be responsible for the uptake of antigens, while the other non-ciliated cell may be involved in the production of the secretory component and the passage of secretory IgA.Supported by a research grant from the Nederlands Astma Fonds