Pulmonary immune effector cells: II. Antigen-specific blastogenic responsiveness of lymphocyte populations during pulmonary immune complex disease in guinea pigs

A guinea pig pulmonary immune complex disease was used to evaluate local antigen (ovalbumin)-specific lymphoproliferative responses in lung tissue, bronchoalveolar spaces, and hilar lymph nodes (HLN) at various time intervals after challenge. The responses of lung tissue and bronchoalveolar lymphocytes appear to be mediated by T cells, whereas the response of HLN lymphocytes was mediated by B and/or T cells, depending on the stage of the disease. The blastogenic response of HLN lymphocytes to concanavalin A was much greater than that observed in lung tissue or bronchoalveolar lymphocyte preparations, even after the removal of adherent cells, suggesting a possible inherent difference between these cell populations in their response to mitogen. This study demonstrates that lung tissue, bronchoalveolar, and HLN lymphocytes are not only capable of responding blastogenically to specific antigen, but that this responsiveness varies throughout the course of the disease. The lymphoproliferative responses and concurrent changes in the proportion of pulmonary immune effector cells are discussed in relation to cellular immunoregulation during the in vivo progression of this pulmonary immune complex disease.     

Localization of the immune response in sarcoidosis.

Pulmonary sarcoidosis is an interstitial disease characterized by granulomas within the lung parenchyma, anergy to a variety of skin tests, and decreased numbers of circulating T-lymphocytes. To evaluate the effector cell populations present at sites of disease in patients with active pulmonary sarcoidosis, inflammatory and immune effector cells were isolated from lung via bronchoalveolar lavage and compared to comparable cell populations from the peripheral blood of the same patients and similar cell populations of normal subjects and patients with idiopathic pulmonary fibrosis. Patients with sarcoidosis had a marked increase in the percentage of T-lymphocytes in the lung despite a significant peripheral blood T-lymphocytopenia. In addition, many of these T-lymphocytes demonstrated surface marker characteristics associated with lymphocyte activation, and they spontaneously secreted leukocyte inhibitory factor. In contrast to patients with sarcoidosis, normal subjects and patients with idiopathic pulmonary fibrosis had similar percentages of T-lymphocytes in lung and blood, and there was no evidence for T-lymphocyte activation. Analysis of lymphocytes in uninvolved marrow from 7 of 8 patients with sarcoidosis revealed proportions of T-lymphocytes similar to those in the marrows of normal subjects and patients with idiopathic pulmonary fibrosis. In comparison, one patient with sarcoidosis had large numbers of T-lymphocytes in bone marrow, but only in areas where there were granulomas in the marrow. These studies suggest that: (1) the alveolitis of pulmonary sarcoidosis is characterized by large numbers of activated T-lymphocytes, and (2) there is an anatomic localization of the immune response in sarcoidosis in that analysis of uninvolved tissues such as peripheral blood may not reflect local immune responses at sites of granuloma formation.     

Traffic of T and B lymphocytes in the normal spleen.

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: Te lymphocytes are found especially in the periateriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous 51Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30% of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periateriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.     

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesis in vivo

Both allogeneic immunocompetent CD4+ lymphocytes and activated macrophages of mice can induce neovascularization when inoculated intradermally into host animals. Because sarcoidosis is associated with an increase in both activated macrophages and CD4+ effector lymphocytes in the lung, we carried out experiments in which cells obtained by bronchoalveolar lavage (BAL) of patients with pulmonary sarcoidosis were tested in a murine intradermal angiogenesis assay. BAL cells from patients with pulmonary sarcoidosis induced a significantly greater degree of angiogenesis than those from normal volunteers or from patients with other lung diseases. Moreover, the degree of angiogenesis induced by BAL cells from patients with sarcoidosis correlated positively with the severity of the disease. When BAL cells were separated into macrophage and lymphocyte subpopulations by flow cytometric techniques, the observed angiogenic activity was restricted primarily or exclusively to macrophages; lymphocytes were unable to induce angiogenesis in this xenogeneic assay system. These experiments suggest that pulmonary macrophages may play a role in the pathogenesis of sarcoidosis by inducing changes in the pulmonary microvasculature. Moreover, we hypothesize that these vascular changes may be induced not only in the lung but also in other organ systems such as skin, muscle, and eye in which microangiopathies are associated with sarcoid disease.     

Extrahepatic manifestations in transgenic mice of osteopontin in hepatocytes-A clue to advent of pathological state in various organs of chronic hepatitis C patients.

Osteopontin is a cytokine essential for initiation of Th1 immune reaction. We established transgenic mice expressing osteopontin in hepatocyte, in which liver necrosis with lymphocyte infiltration developed gradually from 12 weeks of age with up-regulated osteopontin levels in the circulation, suggesting that extrahepatic manifestations might also occur as a result of excessive Th1 immune reaction. We examined histological and immunohistochemical features of various organs in these mice. Splenomegaly and enlargement of lymph nodes around the liver and intestine became apparent with marked infiltration of small lymphocytes in the transgenic mice later than 24 weeks of age. Immunostaining revealed that lymphocytes in the spleen and lymph nodes were positive for either CD3 or CD20, suggesting that the infiltrating lymphocytes were both B and T cells. Similar lymphocyte infiltration was found in the lung, kidney and submandibular gland. Alveolar septa became hypertrophic with lymphocyte infiltration, and the lung showed the appearance of interstitial pneumonia. These lesions are similar to extrahepatic manifestations in chronic hepatitis C patients, suggesting that augmented Th1 immune reaction to hepatitis C virus (HCV) proteins or the proteins with molecular mimicry of HCV may be a contributing factor for the formation of the pathological state not only in the liver but also in various organs under chronic infection of hepatitis C virus.     

Experimental study on the influence of alginate induced immune complex on BALF cells

Immune complex containing alginate and antialginate antibodies plays an important role in the disease-progress of chronic airway infection with mucoid-alginate producing strains. For the purpose of clarifying the immune-pathogenic influence of the alginate induced immune complex (alg-IC) on inflammatory cells in bronchoalveolar lavage fluid (BALF), an experimental study was performed. The alginate immunized mice were injected through the trachea with alg-IC extracted from the immunized mouse serum in advance, and the changes in BALF-cells, such as macrophage, neutrophil, lymphocyte, CD16/32 positive neutrophil, CD4+ lymphocyte, CD4+CD45+ lymphocyte, CD8+ lymphocyte, CD8+CD11b- lymphocyte were investigated along with the passage of time as compared with those of the non-immunized mice. 1) On the 2nd day after intratracheal injection, the time which was chosen as an acute phase, the total count of macrophages, neutrophils, lymphocytes were increased in both groups. However CD16/32 positive neutrophil (with the expression of Fc-gamma recepter on it) was significantly decreased in the immunized group. 2) On the 5th day being chosen as the resolving phase of acute inflammation, the number of the increased inflammatory cells tended to recover to the base line value in both groups. But the continuous decrease in CD16/32 positive cell and the significant increase in CD4+CD45+ lymphocytes were found in only the immunized group. 3) On the 16th day being chosen as the beginning of the chronic phase, all inflammatory cells investigated in the non-immunized group recovered to the base line level. In the immunized group, however, significantly higher values of neutrophil-count still remained, in spite of the decrease in CD 16/32 positive neutrophils. Also, CD4+CD45+, CD8+, CD8+CD11b- lymphocytes were significantly at a higher level. 4) Histological findings in the lung tissue was supported the above findings. 5) From the above, in the alginate immunized group, the scavenging function of neutrophils for the alg-IC deposited in lung tissue would be suppressed resulting from the decrease in CD16/32 positive neutrophils, in spite of the increase in total count of neutrophils. Consequently, long term deposition of alg-IC in the lung would induce an accumulation of cytotoxic CD8+ T lymphocyte or other lymphocytes as one of the cell-mediated immune responses. This indicates that such a harmful immune reaction induced by alg-IC leads the chronic infection with mucoid-alginate producing pathogens to be more intractable.     

Traffic of T and B Lymphocytes in the Normal Spleen

The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: T^E lymphocytes are found especially in the periarteriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous ⁵¹Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30 % of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periarteriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.     

严重急性呼吸综合征的肺组织损伤病理改变

目的 观察严重急性呼吸综合征(SARS)死亡患者的肺部病变特点。方法 采用光镜、组织特殊染色对3例SARS死亡患者的肺组织进行了重点观察。采用兔抗-Fas、鼠抗-PCNA、鼠抗-CD83、CD4、CD8单克隆抗体，经免疫组织化学法对肺及肺门淋巴结等组织进行了检测。结果 肺脏的外观多呈红色或紫红色，镜下显示不同程度的间质渗出性或漏出性炎症和肺泡损伤，肺泡间隔内单个核细胞浸润，肺泡腔内有透明膜形成及凋亡脱落的Ⅱ型肺泡上皮细胞。一些肺泡毛细血管腔内可见纤维素性血栓形成，支气管动脉腔内有血栓栓塞。增宽的肺泡间隔内有纤维素沉积。3例肺泡腔内未见明显地巨细胞浸润。免疫组织化学检测显示，增殖细胞核抗原阳性细胞少见，Ⅱ型肺泡上皮细胞及肺泡间隔、肺门淋巴结内的单个核细胞有较多的Fas抗原表达；与慢性炎性淋巴结相比，SARS患者的肺门淋巴结内淋巴细胞结构破坏、淋巴细胞稀疏、数量明显减少，但CD83及CD8阳性细胞仍较多见，而CD4阳性淋巴细胞少见。脾脏也可观察到淋巴细胞数量的减少，白髓萎缩，出血坏死，表达CD4的阳性细胞减少。结论 严重的肺组织及免疫系统损伤可能导致SARS患者的死亡。     

Plasma-lymph albumin kinetics, total lymph flow, and tissue hematocrit in normally hydrated dog lungs

Lung lymph flow was normalized for lung weight and total lung lymph flows were calculated in five mongrel dogs using a kinetic analysis of albumin distribution between the pulmonary capillaries, interstitial fluid, and pulmonary lymph. Using prenodal tracheobronchial lymph an intravenous bolus of 125I-labeled albumin equilibrated between plasma and lymph with mean T1/2 of 2 hr 22 min. The mean volume of interstitial fluid drained by the cannulated lymphatics was 9.9 ml which corresponded to the extravascular albumin distribution volume of 31% of the total lung weight. Lung tissue hematocrit was determined using 51Cr-labeled red cells and 125I-albumin and averaged 92% of the simultaneous mixed venous hematocrit. The extravascular albumin and 99mTc-DTPA (diethylenetriamine pentacetic acid) spaces in lung were corrected for differences between tissue and mixed venous hematocrit and were 18.5 and 33.0 ml/100 g, respectively. This indicated that albumin distributed in 57% of the interstitial volume at 4 hr after injection. Lung lymph flow normalized to postmortem lung mass during baseline conditions was 0.060 ml/min/100 g after correction for tissue hematocrit differences. Normalized lymph flows are used for quantitative comparisons of lung lymph protein flux data between different types of experiments.     

Localized pulmonary neutrophil influx induced by lung lavage in sheep

The kinetics and distribution of neutrophil (PMN) influx into lung air spaces subsequent to bronchoalveolar lavage (BAL) were studied in adult sheep. The concentration of PMNs in BAL fluid peaked at 6 h and remained elevated for 48 h after the initial lavage. The response was observed primarily in the lung segment originally lavaged although minor changes were seen in BAL from immediately adjacent regions. No response was observed in the contralateral lung. Except for a transient decrease in pulmonary alveolar macrophages and monocytes at 6 h, changes in mononuclear cell populations (pulmonary alveolar macrophages, monocytes and lymphocytes) were minimal.     

The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function

A murine model of acute pulmonary histoplasmosis was employed to study the pathogenesis of the disease process by means of histopathology, bronchoalveolar lavage, and respiratory function tests. These studies were performed on C57BL/6 mice from 8 h to 8 wk after intranasal inoculation of 10(5) yeast forms of Histoplasma capsulatum and on age-matched control animals that received saline only. At Week 1, the histopathology was characterized by subacute inflammation consisting of polymorphonuclear leukocytes (PMN), lymphocytes, and macrophages that infiltrated the interstitium around small bronchioles and adjacent alveoli. At Weeks 2 and 4, the infiltrates were comprised predominantly of lymphocytes and macrophages; noncaseating granulomas were present at Week 2. Aggregates of lymphoid cells were prominent along the bronchial tree and in perivascular distribution. Those in close contact with bronchiolar epithelium resembled hyperplastic bronchus associated lymphoid tissue. Quantitative studies of cells in the BAL fluid revealed a large influx of PMN at Week 1 with return to normal range by Week 2. At this time there was a significant (p less than 0.02) increase in lymphocytes that persisted through Week 8, although histopathologic changes were minimal in lung at this time. A significant decrease in the DLCO/TLC at Week 2 in association with a normal vital capacity indicated impairment of respiratory function secondary to the alveolitis induced by H. capsulatum infection rather than a reduction of lung volume. This model offers promise for additional correlative studies of lymphocyte subsets in lung tissue and alveolar spaces as well as of the functions subserved by these respective populations.     

孟鲁司特钠对哮喘大鼠肺组织、脾脏、胸腺NF-κB mRNA表达的影响及病理变化的研究

目的观察白三烯受体拮抗剂孟鲁司特钠对哮喘大鼠肺组织、脾脏、胸腺NF-κB mRNA的表达及病理变化的影响。方法建立哮喘大鼠模型后,将动物随机分成三组,正常对照组、哮喘组、孟鲁司特钠组。干预后处死动物,用原位杂交法检测肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达及光镜观察肺组织、脾脏的病理变化。结果与正常对照组比较,哮喘组大鼠肺组织气道周围炎症明显,肺泡隔增宽。脾脏白髓淋巴细胞区中度增生。孟鲁司特组肺组织气道周围炎症减轻,肺泡隔增宽有所减轻,脾脏白髓淋巴细胞区轻-中度增生。哮喘组大鼠肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达增加（P〈0.05）。孟鲁司特钠组大鼠肺组织、脾脏、胸腺淋巴细胞中NF-κB mRNA的表达受抑（P〈0.05）。结论孟鲁司特钠在支气管哮喘的发病机制中有一定的抗炎作用。     

Expression of Ia by murine alveolar macrophages is upregulated during the evolution of a specific immune response in pulmonary parenchyma

These studies were performed to test the hypothesis that the evolution of a specific immune response in lung parenchyma upregulates the expression of Ia on surface membranes of murine alveolar macrophages. A secondary antibody-forming cell response to sheep erythrocytes was generated in lung parenchyma by intratracheal antigen challenge of systemically primed mice. During the immune response, alveolar macrophages were retrieved by bronchoalveolar lavage, and the percentages and total numbers of Ia-positive macrophages were measured by indirect immunofluorescence. The expression of Ia on surface membranes of lavaged alveolar macrophages increased in association with the generation of antibody-forming cell responses in lung tissue. This increase in Ia expression was antigen specific; intratracheal challenge with noncrossreacting antigen did not increase Ia expression. Nonspecific inflammation of the lung, induced by intratracheal hydrochloric acid, elicited increases in total numbers of macrophages that were similar in magnitude to those induced by specific immune responses, but increased Ia expression only modestly. In unprimed mice, intratracheal antigen challenge did not increase Ia expression by alveolar macrophages unless the mice had received immune splenocytes by adoptive transfer at the time of challenge. The results show that the generation of a specific immune response in pulmonary parenchyma upregulates the expression of Ia by murine alveolar macrophages in vivo and suggest that the accumulation of antigen-reactive lymphocytes in the lung plays an important role in this upregulation.     

Pulmonary tissue resistance to Candida albicans in normal and in immunosuppressed mice

We characterized the clearance of Candida albicans from the lung using a murine model for pulmonary aspiration. Swiss Webster mice uniformly survived intratracheally administered boluses of C. albicans (1 to 30 X 10(5) colony-forming units of yeast) which killed the majority of mice (more than 85%) when injected intravenously. Clearance studies, using quantitative cultures of lung homogenates, demonstrated rapid elimination of C. albicans from the lung after a 6-h delay; the residual fractions of viable fungi were 8.3 and 0.7% of the initial inoculums at 24 and 48 h, respectively, after inoculation. The number of leukocytes in the bronchoalveolar spaces increased twofold to threefold after deposition, and this primarily reflected a neutrophil influx. Histologic studies supported the bronchoalveolar lavage results and revealed a diffuse interstitial neutrophilic infiltrate and clusters of inflammatory cells in air spaces at 6 and 24 h after Candida deposition. Examination of lavage pellets demonstrated that both neutrophils and macrophages ingested C. albicans in vivo. Immunosuppression (orally administered prednisolone for 2 wk) delayed the clearance of C. albicans from the lung. However, evaluation of neutrophil migration into bronchoalveolar spaces and of the in vivo ingestion capacity of both macrophages and neutrophils did not identify differences that could explain this delayed clearance in steroid-treated mice. The fungicidal activity of pulmonary leukocytes was measured with in vitro assays and was similar in phagocyte cultures from control and steroid-treated mice. In summary, intrinsic pulmonary defense factors and recruited neutrophils rapidly and completely clear C. albicans from the lung after bolus deposition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Splenectomy selectively affects the distribution and mobility of the recirculating lymphocyte pool

The spleen plays a major role in immune surveillance, but the impact that splenectomy exerts on the immune competence of an individual is not fully resolved. Here we show that neonatal splenectomy in sheep does not abrogate the development of a large, nonrecirculating pool of lymphocytes and that it has no effect on the acquisition of a normal blood lymphocyte profile. Splenectomy did, however, result in a significant decrease in blood residency time of recirculating lymphocytes and in an enhanced accumulation of recirculating lymphocytes in lymph nodes. Furthermore, nonrecirculating peripheral blood lymphocytes were less likely to migrate to the lung, possibly because of saturation of the marginal pool by recirculating lymphocytes. Although splenectomy has little effect on the development or distribution of lymphocyte subsets in blood and lymph, it has marked effects on the rate of recirculation of lymphocytes, which may have significant implications for peripheral immune surveillance in patients who undergo splenectomy.     

Oral administration of cyclosporin does not prevent expansion of antigen-specific,gut-associated,and spleen lymphocyte populations duringChlamydia trachomatis proctitis in nonhuman primates

To study the effects of oral cyclosporin (CsA) administration on immune responses in the gastrointestinal tract, humoral and cellular immune responses were studied in CsA-treated nonhuman primates having Chlamydia trachomatis proctitis (lymphogranuloma venereum, LGV). There was no apparent effect of CsA treatment on the gross or microscopic appearance of LGV proctitis, but CsA-treated animals, with or without LGV infection, had lymphoid hyperplasia of spleen and mesenteric lymph nodes. CsA treatment inhibited the primary antibody response to LGV, inhibited peripheral blood lymphocyte mitogen-induced proliferation and IL-2 production, and inhibited LGV-specific proliferation of peripheral blood lymphocytes. In contrast, mitogen-stimulated proliferation of spleen, mesenteric lymph node, and lamina propria lymphocytes was not significantly inhibited in CsA-treated animals. In addition, LGV-specific proliferation of spleen and mesenteric lymph node lymphocytes was not inhibited. High mitogen-stimulated IL-2 production of lamina propria lymphocytes was only partially inhibited in CsA-treated animals. In vitroCsA treatment had the expected inhibitory effects on mitogen- and antigen-induced proliferation of spleen and mesenteric lymph node lymphocytes. Thus, although oral cyclosporin inhibits the antibody and proliferative responses of peripheral blood lymphocytes to antigens and mitogens in animals having Chlamydia trachomatis proctitis, it does not prevent the expansion of antigen-specific, gut-associated, and spleen lymphocyte populations.Part of this work has been published as a preliminary report in abstract form (Clinical Research 34:446A, 1986).     

Prognostic role of eosinophils in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD) are chronic inflammatory lung disorders which may be characterized in various subgroups of patients by increased numbers of macrophages, neutrophils, lymphocytes, and/or eosinophils. Previous studies have suggested that the cell populations recovered with bronchoalveolar lavage (BAL) may be important in predicting disease progression and response to therapy. We evaluated this hypothesis in 27 patients by determining if the cell populations recovered with BAL differed between patients who improved, remained stable, or worsened in their pulmonary functions (as defined by at least a 15 percent change in forced vital capacity) over a six-month observation period. The findings suggested that BAL eosinophilia may be a marker of progressive lung disease in patients with IPF and PF-CVD.     

Murine malaria: cellular interactions in the immune response

The cellular and humoral interactions that contribute to protective immunity in Plasmodium yoelii malaria were studied by adoptive transfer of selective cell populations or hyperimmune serum into sublethally irradiated syngeneic C57BL/6 mice. For some experiments pools of mononuclear spleen cells were depleted of T or B lymphocytes and cells that take up silica were inactivated by standard procedures. Unfractionated immune spleen cells, but not nonimmune spleen cells, protected recipients from lethal P. yoelii challenge. Analysis of the protective capacity of subpopulations of immune spleen cells showed that levels of immunity similar to those seen after transfer of unfractionated immune cells were present only in those instances where immune macrophages, i.e., cells not previously inactivated with silica, were transferred concomitantly with either immune T (supplemented with nonimmune B) or immune B (supplemented with nonimmune T) cells. The requirement for immune macrophages could not be met by transferring mononuclear cells from a nonimmune donor. The results support the hypothesis that an immune 5,000 R-radioresistant, silica-inactivated, non-T, non-B cell, probably a macrophage, must act in concert with immune T and B lymphocytes in the optimal expression of transferred immunity to P. yoelii.     

Chronological assessment of asbestos exposure on cell composition in murine lung.

To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber.     

成人纵隔和肺部淋巴结结核破溃后的CT表现及其治疗转归分析

目的 探讨成人纵隔和肺部淋巴结结核破溃后的CT表现特点并对其治疗转归进行分析。 方法 搜集广州市胸科医院2009年1月至2017年12月收治的成人纵隔和肺部淋巴结结核并发破溃的52例患者进行回顾性分析。根据病变淋巴结破溃的位置而将其分成3组:只向气管支气管内破溃为气管支气管组39例;只向肺内破溃为肺组13例;同时向气管支气管和肺内破溃为气管支气管-肺组20例。分析各组患者的CT表现征象,总结破溃淋巴结的治疗转归情况。 结果 52例患者共有84个破溃淋巴结。气管支气管组共23个淋巴结,14个肿大淋巴结并相应支气管水肿增厚的黏膜、肉芽局部向支气管腔内呈结节状突出,CT增强扫描示13个淋巴结坏死区向气道内突出,1个为均匀强化表现,其余9个淋巴结相应瘘口侧的气道壁欠光滑但无结节征象。肺组共13个淋巴结,肿大淋巴结跨纵隔-肺、肺门-肺组织形成结节状或者肿块状,肺内病灶周围可见晕征或斑片状模糊影,CT增强扫描示12个淋巴结呈环形或分隔样强化,其内坏死区局部向肺组织内延伸,1个呈均匀强化。气管支气管-肺组患者共48个淋巴结,并发纵隔及肺门多区域多淋巴结明显肿大,其中11个向气道内、20个向肺组织内突出,CT增强扫描示后淋巴结内坏死区向瘘口侧突出,除了1个均匀强化,其余16个淋巴结相应瘘口侧的气道壁欠光滑但无结节征象。经抗结核药物、向气道内破溃的淋巴结同时经支气管镜钳取肉芽肿、抽吸坏死物等治疗,患者遗留瘘口处支气管狭窄33例,肺内遗留瘘口相关的纤维硬结灶18例。 结论 成人纵隔和肺部淋巴结结核发生破溃,以向气管支气管内、肺内破溃为主,CT平扫及增强有助于其早期诊断;破溃的纵隔和肺部淋巴结结核治疗后有一定效果,但部分患者遗留不同程度的支气管瘢痕性狭窄。