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T Tschernig

Publications and source records attributed to T Tschernig.

65 records · Page 4Linked to original sources
PubMed1997

Conductive airway surfactant: surface-tension function, biochemical composition, and possible alveolar origin.

Alveolar surfactant is well known for its ability to reduce minimal surface tension at the alveolar air-liquid interface to values below 5 mN/m. In addition, it has been suggested that an analogous conductive airway surfactant is also present in the airways. To elucidate the composition, possible origin, and surface activity of conductive airway phospholipids (PL), we compared in adult porcine lungs the PL classes and phosphatidylcholine (PC) molecular species of nonpurified tracheal aspirate samples with those of bronchoalveolar lavage fluid (BAL), tracheobronchial epithelium, and lung parenchyma. We also analyzed PL and PC composition, protein content, and surface activity of surfactant isolated from tracheal aspirates (SurfTrachAsp), BAL (SurfBAL), and the 27,000 x g pellet of BAL (SurfP27000) by density-gradient centrifugation. Although PL composition revealed contributions of the airways to tracheal aspirates, the composition of PC molecular species of tracheal aspirates was similar to that of BAL and lung parenchyma, but differed considerably from that of airway epithelium. SurfTrachAsp had the same PL and PC composition as SurfBAL and SurfP27000, indicating that this fraction of tracheal aspirates may have originated from the alveoli. Nevertheless, minimal and maximal surface tensions were higher in SurfTrachAsp than in SurfBAL and SurfP27000. Analysis of surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) revealed that SP-A was decreased and SP-B and SP-C were absent, whereas total protein was increased in SurfTrachAsp. We conclude that as compared with alveolar surfactant, PL of SurfTrachAsp show the same composition, but that surface-tension function is impaired and the concentration of surfactant proteins is decreased in SurfTrachAsp.

Analysis of Variance↗
PubMed1997

The lung as a source and a target organ for T- and B-lymphocytes.

In lung transplantation, a substantial number of donor leukocytes are transferred from the donor to the recipient by the graft. Using a rat model, it was analyzed in this study to what extent leukocytes leave the lung, to which phenotype they belong, and to which organs they migrate. The model used was the orthotopic transplantation of the left lung of LEW.7B(RT7b) rats into LEW(RT7a) recipients. Lung allografts are not rejected in this strain combination, which differs only in the RT7 system, a genetic polymorphism of CD45. Using the RT7b marker (monoclonal antibody His41), the distribution of donor leukocytes passively transferred with the graft was studied by immunohistology 2 wk after transplantation. At this time, 2.9 +/- 0.1% (n = 6) of the peripheral blood leukocytes in the recipients were derived from the donor lung. The donor cell population detected in the blood consisted of T cells (59 +/- 4%), B cells (5.1 +/- 0.2%) and a surprisingly high fraction of natural killer (NK) cells (36 +/- 3%). No monocytes or granulocytes were found. In lymph nodes, spleen and thymus donor-derived T- and B-cells could be shown in typical T- and B-areas, respectively. Donor-derived leukocytes were found in the liver and the skin. In the tissue and the bronchoalveolar lavage (BAL) of the host lung, predominantly T cells were found. Furthermore, in the donor tissue and BAL more than 70% of T- and B-cells were host type, demonstrating that the donor lung had been repopulated to a great extent by host lymphocytes. This supports the relevance of BAL as a diagnostic tool in lung diseases. Thus, the lung is an immunologically important site, releasing lymphocytes which migrate to other organs and also attracting many lymphocytes from the circulation.

Animals↗
PubMed1996

Both activated and nonactivated leukocytes from the periphery continuously enter the thymic medulla of adult rats: phenotypes, sources and magnitude of traffic.

Although the thymus is primarily noted for the export of T cells to the periphery, a small influx of cells has also been observed. It is still a matter of debate whether entry into the thymus depends on prior activation. The phenotypes, sources and degree of immigration are largely unknown. We monitored by quantitative immunohistochemistry the entry of cells from the periphery into the rat thymus in three experimental models. We injected i.v. recirculating, small, nonactivated CD4+ T cell subsets, often referred to as naive (CD45RC+) and memory or antigen-experienced (CD45RC-) cells, purified from thoracic duct lymph of allotype-marked donors, allotype-marked leukocytes released from spleen or lung transplants, or leukocytes labeled in the periphery for 12 weeks during the S-phase of the cell cycle by oral application of 5-bromo-2-deoxyuridine (BrdUrd). Early after i.v. injection (0.5 h), significantly more antigen-experienced (CD45RC-) CD4+ T cells entered the thymus, and by 24 h four times as many cells from the CD45RC- subset as from the CD45RC+ subset had entered the thymus and localized to the medulla. None of the thymic entrants expressed the interleukin (IL)-2 receptor. Following spleen transplantation approximately 40% of donor cells entering the thymic medulla were T cells and approximately 55% were B cells. In contrast, from a lung transplant, approximately 85% of peripheral immigrants were T cells and approximately 10% were B cells. After both procedures, a small number of NK cells and monocytes/macrophages were found among the immigrants (< 5%). Rats were fed BrdUrd continuously for 12 weeks, a procedure which labeled approximately 30% of peripheral lymphocytes but not cortical thymocytes. BrdUrd-labeled cells were localized almost exclusively to the thymic medulla and represented approximately 10% of medullary cells. Of the thymic immigrants approximately 50% were T cells, approximately 30% were B cells (including approximately 15% IgD+ cells), approximately 15% were NK cells and the remainder (approximately 5%) were monocytes/macrophages. Only a quarter of BrdUrd-labeled cells expressed the IL-2 receptor. The thymus is continuously infiltrated by both activated and nonactivated leukocytes from the periphery, including T cells, B cells, NK cells and monocytes. These immigrants are supplied by lymphoid and nonlymphoid organs in a characteristic subset composition. Their entry is facilitated by prior antigen experience or activation. Thus, the participation of the thymic medulla in general leukocyte traffic suggests a mechanism by which the T cell repertoire could potentially be modulated by the peripheral tissues.

Animals↗
PubMed1995

Lymphocytes in the lung: an often neglected cell. Numbers, characterization and compartmentalization.

The lung is continuously in contact with inhaled particles, some of which are of microbial origin. This requires adequate defence mechanisms in the form of immune reactions. These can be subdivided into the afferent and efferent limb. Specific immune reactions depend on the interactions between lymphoid and accessory cells. Therefore, the local histotopographic localization of lymphocyte subsets has to be known to understand pulmonary immune reactions. As lymphocytes have often not been mentioned when cells in the respiratory tract have been characterized, their compartmentalization, number and subset composition in the lung are outlined here. Lymphocytes are found in the epithelium and lamina propria of the bronchi with different subset compositions. In some species, like the rabbit, bronchus-associated lymphoid tissue (BALT) is found as follicle-like aggregations with lymphocytes infiltrating the epithelium, which shows specialized epithelial cells. BALT, however, is not a constitutive structure in all species, e.g. in humans. Nevertheless, certain (probably) microbial stimuli can induce BALT in adult humans. In contrast to many other organs, the lung vascular bed contains large numbers of lymphocytes. Little is known about the adhesion molecules that make this margination possible. In the lung interstitium about 10 x 10(9) lymphocytes have been calculated for healthy adults. The most easily accessible pool of lymphocytes in the human lung are those recovered by bronchoalveolar lavage. The vast majority of such lymphocytes express markers typical for "memory lymphocytes". The intrapulmonary migratory routes of lymphocytes and the integration of the lung in the common mucosal immune system are described.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Bronchus-associated lymphoid tissue (BALT) in the lungs of children who had died from sudden infant death syndrome and other causes.

BACKGROUND: Bronchus-associated lymphoid tissue (BALT) is well characterised in rabbits and rats. In humans, however, it does not seem to be present in the healthy adult lung, although it can develop after certain microbial stimulation. METHODS: In the present study a consecutive series of lungs from 88 children who had died of sudden infant death syndrome (SIDS) and 34 control cases of comparable age were examined for the presence of BALT. RESULTS: BALT was present in 36.4% of the patients who had died of SIDS and in 44.1% of the control cases. The probability of finding BALT increased with age, with similar kinetics in both groups. CONCLUSIONS: Future studies need to define when and at what rate BALT disappears as children get older. In young children BALT may act as an entry site for antigens to initiate an immune response, as is well documented for the gut-associated lymphoid system.

Age Factors↗
PubMedDate not supplied

Bronchus-associated lymphoid tissue (BALT) is not present in the normal adult lung but in different diseases.

Bronchus-associated lymphoid tissue (BALT) was first described in the lungs of rabbits and differs greatly between species. It is part of the integrated mucosal immune system. This review clarifies its morphological definition and focuses on the situation in humans. The frequency of BALT at different ages, after chronic stimulation and in different diseases is described. In healthy humans, BALT can only be found in the lungs of children and adolescents. The role of BALT in lung transplantation and in the development of low-grade malignant lymphomas in the airways is also discussed. Furthermore, questions concerning the inducibility of BALT as an entry site for vaccines, and the regulation of its activity for future therapeutic interventions in pulmonary immune reactions are addressed.

Adolescent↗
PubMedDate not supplied

Residual cftr expression varies with age in cftr(tm1Hgu) cystic fibrosis mice: impact on morphology and physiology.

Mouse models for cystic fibrosis (CF) mimic intestinal manifestations of the human disease, but the lung disease phenotypes are lacking in most strains. In this work, the issue was addressed whether aging of the respiratory tract leads to lung pathophysiology in the exon 10 insertional mutant cftr(tm1Hgu) mouse. Weight gain, body weight and life-span of cftr(tm1Hgu) mice were significantly reduced compared with control mice. cftr(tm1Hgu) mice expressed 20, 21 or 37% (median) of wild-type cystic fibrosis conductance transmembrane regulator (cftr) mRNA transcript in lungs, intestine and kidney. Wild-type cftr mRNA in renal and respiratory epithelia varied with age from levels similar to Ztm:MF1 controls at the age of 2 and 4 months to levels seen in patients with CFTR splice mutations beyond the age of 6 months. The morphology of the bronchi and more distal airways was apparently normal in cftr(tm1Hgu) mice during their first year of life. The alveolar surfactant phospholipid pool was increased in cftr(tm1Hgu) mice by 1.5- to 2-fold compared with Ztm:MF1 controls. Alveolar clearance of gamma-labelled scandium oxide - the first report of lung clearance measurement in living mice - was reduced in cftr(tm1Hgu) mice compared with littermate controls. Although no progressive lung pathology was seen in the cftr expression of cftr(tm1Hgu) mice, surfactant phospholipid homeostasis, and alveolar and mucociliary clearance were abnormal. Therefore, the described model is useful for studying the initial CF lung pathophysiology.

Aging↗
PubMedDate not supplied

Recruitment of lymphocytes and dendritic cells from the blood to the bronchoalveolar space and the draining lymph nodes after a single intrabronchial application of the lipopeptide MALP-2.

OBJECTIVE: It has been shown previously that the synthetic macrophage-activating lipopeptide, MALP-2, is a potent stimulator of the respiratory immune system and an effective adjuvant in the induction of mucosal immune responses. In this study, the migration route of leukocytes from the blood to the bronchoalveolar space and then to the draining lymph nodes was investigated. METHODS: MALP-2 was intratracheally instilled into lungs of Lewis rats. Bronchoalveolar lavage cells as well as cell preparations of other lung compartments such as the marginal vascular pool, the interstitial pool and also the draining lymph nodes were examined 3 days later. RESULTS: The application of MALP-2 induced a pronounced leukocyte accumulation in the bronchoalveolar space and the lung interstitium but not in the marginal vascular pool. A tendency to increased lymphocyte and dendritic cell numbers was observed in the draining lymph nodes. CONCLUSION: Our data indicate the migration of blood cells into the lung interstitium and the bronchoalveolar space in response to MALP-2. Thus, the immune reaction induced by MALP-2 might be of relevance as an adjuvant treatment in inhalant vaccination strategies in the lung.

Animals↗
PubMedDate not supplied

Stimulation of bronchus-associated lymphoid tissue in rats by repeated inhalation of aerosolized lipopeptide MALP-2.

OBJECTIVE: Bronchus-associated lymphoid tissue (BALT) is a part of the integrated mucosal immune system. It may play an important functional role for antigen uptake and induction of specific immune reactions. The aim of this study was to investigate whether it is possible to induce or modulate BALT by the repetitive inhalation of the synthetic lipopeptide MALP-2. METHODS: Female Lewis rats (245 +/- 19 g) inhaled 25 microg of MALP-2 six times at intervals of 1 week. One week after the last inhalation, they were sacrificed. Cells of the bronchoalveolar lavage and the left lung were investigated by flow cytometry. The middle lobe of the right lung was embedded in paraffin. BALT was semiquantitatively measured in 15 serial cross sections per animal. RESULTS: After repetitive inhalation of the diluent as well as MALP-2, BALT was found. The total area was increased after repetitive treatment with MALP-2. In addition, the preferential incidence of BALT was higher after MALP-2 application, in association with a bronchial diameter of 0.6-1 mm. The cellular analysis revealed no differences in the number of leukocyte subsets between the control and MALP-2 group. CONCLUSION: MALP-2 is a potent local stimulator and can be used to modulate BALT by repetitive inhalant treatment. The functional significance of enlarged or activated BALT has to be elucidated in future studies.

Adjuvants, Immunologic↗
PubMedDate not supplied

Comparison of lymphocyte subsets, monocytes, and NK cells in three different lung compartments and peripheral blood in the rat.

Investigations on leukocyte populations in the lung have shown that lymphocytes are found in different anatomical compartments. Lymphocytes can be seen to a different extent in the lung interstitium, the epithelium and lamina propria of the bronchi, the bronchoalveolar space, and the marginal lung vascular bed. Previous studies focused on one compartment only, or a mixture of leukocytes from lung homogenates were prepared. This study compared cellular yields from the lung parenchyma, the bronchoalveolar space, and the perfusate of the lung vasculature of healthy male Lewis rats. All compartments were investigated in the same animal, and seven different lymphocyte subsets, monocytes, and natural killer (NK) cells were analyzed using flow cytometry. It was found that the perfusate contained a high proportion of CD4+ lymphocytes compared to the lung interstitium. A very high proportion of CD4+ lymphocytes in the bronchoalveolar lavage (BAL) expressed markers for "memory" T cells. Compared to the blood, the percentage of B and T cells was much lower in the perfusate, whereas the NK cells and monocytes were more frequent. Analysis of leukocyte subsets within all compartments revealed specific, distinguishable cell compositions. Extraction of interstitial lung cells was performed using two different methods. Enzymatic digestion of the lung tissue was compared with a mechanical disruption method. Hardly any differences were observed between the two methods regarding the distribution of lymphocyte subsets, monocytes, and NK cells. These data document the need to study more than one compartment before extrapolating to lymphocytes in the lung in general. Furthermore, changes in numbers of leukocytes and subsets can now be studied in models of lung infections and immune reactions, including the entry from the blood and intrapulmonary migration from one lung compartment to the other.

Animals↗