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Biomedical subjects

A J Hance

Publications and source records attributed to A J Hance.

At least 37 records · Page 2Linked to original sources
PubMed1997

Characterization of proliferative responses and cytokine mRNA profiles induced by Vespula venom in patients with severe reactions to wasp stings.

The reasons why severe allergic reactions to bee and wasp stings develop in only a small portion of exposed individuals are incompletely understood, but differences in T cell responses to venom antigens comparing allergic and non-allergic individuals are likely to be important. To identify such differences, venom-induced proliferative responses and cytokine mRNA production by blood mononuclear cells from Vespula venom-allergic patients and non-allergic individuals were compared. Mononuclear cells from most venom-allergic patients proliferated in response to alkylated Vespula venom (7275 +/- 8387 ct/min, n = 19), and the extent of proliferation was greater for patients with a history of multiple prior stings and those with high levels of venom-specific IgE. Although mononuclear cells from non-allergic subjects showed little or no proliferation in response to venom (926 +/- 711 ct/min, n = 8), production of mRNAs coding for IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-gamma) in response to Vespula venom by cells from non-allergic subjects was detected by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that these individuals had been previously sensitized to venom antigens. In contrast to the Th0 cytokine mRNA profile observed for non-allergic individuals, venom-allergic patients released a more restricted profile of cytokines following stimulation with venom. Only IFN-gamma mRNA expression was detected in all individuals evaluated, whereas IL-2 mRNA was not detected during the first 48 h of stimulation, and T cells from only one of three venom-allergic individuals produced detectable IL-4 or IL-5 mRNA. The difference in cytokine profiles observed comparing venom-allergic patients and non-allergic controls could not be attributed to intrinsic differences in T cells from these individuals, because polyclonal stimulation with phorbol myristate acetate (PMA) + ionophore induced similar cytokine mRNA profiles in the two groups. These studies demonstrate clear differences in the T cell responses of venom-allergic subjects, that may contribute to the development of severe allergic reactions in these individuals.

Adult↗
PubMed1997

Diagnosis of smear-negative pulmonary tuberculosis using sequence capture polymerase chain reaction.

Techniques based on the polymerase chain reaction (PCR) can be used to rapidly identify DNA from Mycobacterium tuberculosis in clinical samples from patients with tuberculosis, but prior studies evaluating this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis have reported poor sensitivity and/or specificity. We have developed a procedure in which mycobacterial DNA in crude samples is specifically captured prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other inhibitors of the amplification reaction (sequence capture PCR). To evaluate the usefulness of this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis, sequence capture PCR was performed prospectively on samples of bronchoalveolar lavage fluid from consecutive patients suspected of having pulmonary tuberculosis but for whom three consecutive samples of respiratory secretions were smear negative. Of the 27 patients evaluated, active tuberculosis was diagnosed in nine; sequence capture PCR was positive for all of these patients, including the three for whom all specimens submitted for culture were negative. No positive results were obtained for lavage fluid from the 18 patients for whom the diagnosis of active tuberculosis was subsequently excluded or 25 additional patients undergoing bronchoalveolar lavage for evaluation of other pulmonary problems, even though many of these patients had a history of prior tuberculosis or radiographic evidence of prior tuberculous infection. Paucibacillary forms of pulmonary tuberculosis can be rapidly identified with high sensitivity and specificity using sequence capture PCR performed on samples obtained by bronchoalveolar lavage.

Adult↗
PubMed1997

Absence of DNA from mycobacteria of the M. tuberculosis complex in sarcoidosis.

To evaluate the role of mycobacterial infection in the pathogenesis of sarcoidosis, several groups have attempted to identify mycobacterial DNA in clinical samples from these patients by polymerase chain reaction (PCR), but widely divergent results have been obtained. It has been suggested that differences in the sensitivity of the procedures used may explain these discrepant results. To test this possibility, the presence of mycobacterial DNA was sought in biopsies from patients with sarcoidosis using sequence capture-PCR, a procedure that is 100-fold more sensitive in detecting mycobacterial DNA in paucibacillary samples than standard PCR protocols. Using this approach, DNA corresponding to two different sequences specific for organisms of the Mycobacterium tuberculosis complex (the 1S6110 insertion element and the DR region) could not be detected in any of the 15 biopsies from patients with sarcoidosis, whereas a high proportion of positive results was obtained for tissue biopsies and other clinical samples from patients with active tuberculosis, including samples that were smear-negative/culture-positive and smear-negative/culture-negative. These results support prior studies suggesting that M. tuberculosis does not play a pathogenic role in sarcoidosis in most patients.

Biopsy↗
PubMed1996

Sequence capture-PCR improves detection of mycobacterial DNA in clinical specimens.

The rapid identification of mycobacterial DNA in clinical samples by PCR can be useful in the diagnosis of tuberculous infections, but several large studies have found that the sensitivity of this approach is not better than that of culture. In order to improve the sensitivity of detection of mycobacterial DNA in clinical specimens from patients with paucibacillary forms of tuberculosis, we have developed a procedure permitting the specific capture of mycobacterial DNA in crude samples prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other potential inhibitors of the amplification reaction (sequence capture-PCR). By using this approach to capture and amplify two different sequences specific for organisms of the Mycobacterium tuberculosis complex (IS6110 and the direct repeat region), it was possible to detect as little as one genome of mycobacterial DNA in samples containing up to 750 micrograms of total DNA, representing a 10- to 100-fold increase in sensitivity compared with that obtained by purifying total DNA prior to amplification. Detection of the IS6110 sequence in pleural fluid samples from patients with tuberculous pleurisy by sequence capture-PCR gave positive results in 13 of 17 cases, including 3 of 3 culture-positive samples and 10 of 14 culture-negative samples. In contrast, when total DNA was purified from these samples by adsorption to a silica matrix prior to amplification, only the three culture-positive samples were positive by PCR. The sensitivity of detection of the direct repeat sequence in these samples by sequence capture-PCR was similar to that of IS6110 and, in addition, permitted immediate typing of the strains from some patients. We conclude that sequence capture-PCR improves the sensitivity of detection of mycobacterial DNA in paucibacillary samples. This approach should be useful in detecting rare target sequences from organisms implicated in other pathologic processes.

Adult↗
PubMed1996

Role of granulocyte-macrophage colony stimulating factor (GM-CSF) in the pathogenesis of adult pulmonary histiocytosis X.

BACKGROUND: Pulmonary histiocytosis X is a disorder characterised by the presence of destructive granulomas preferentially involving distal bronchioles, that contain numerous activated Langerhans' cells. Recent studies have shown that granulocyte-macrophage colony stimulating factor (GM-CSF), which is produced by normal bronchiolar epithelium, may play an important part in the distribution and differentiation of Langerhans' cells. The aim of this study was to evaluate the role of this factor in the pathogenesis of pulmonary histiocytosis X. METHODS: Four patients with pulmonary histiocytosis X were examined by immunohistochemical techniques for GM-CSF and CD1a surface molecules. RESULTS: In early lesions the epithelium of bronchioles affected by the disease was strongly positive for GM-CSF and infiltrated by numerous CD1a+ Langerhans' cells organised into granulomas. In contrast, the expression of GM-CSF was substantially lower in bronchioles not affected by the disease, and these bronchioles contained few Langerhans' cells. When destruction by histiocytosis X lesions was more advanced, only remnants of bronchiolar epithelium could occasionally be identified; these remained strongly reactive for GM-CSF. Langerhans' cells within granulomas also moderately expressed this cytokine. CONCLUSIONS: These results support the hypothesis that GM-CSF could be one of the factors responsible for the local accumulation of lymphostimulatory Langerhans' cells in early lesions of pulmonary histiocytosis X.

Adult↗
PubMed1996

Extensive apoptosis of lung T-lymphocytes maintained in vitro.

The phenotypic and functional properties of T cells recovered from the lung indicate that many of these cells have been recently activated. Because such recently activated cells are often more susceptible to death through apoptotic mechanisms, the viability of lung T cells recovered from bronchoalveolar lavage and those isolated from peripheral blood was compared. The progressive loss of viable cells following in vitro culture was considerably greater for lavage T cells than blood T cells, and was observed for cells from both patients with sarcoidosis and control subjects. Following 4 days of culture, 76 +/- 14% of blood cells, but only 31 +/- 13% of lavage cells from sarcoid patients were viable. The evaluation of morphologic features and flow cytometric profiles, as well as the demonstration of typical oligonucleosomal fragmentation of DNA extracted from these cells indicated that lavage T cells were dying by apoptotic mechanisms. CD4+ T cells appeared to be particularly sensitive to apoptosis. Most lavage T cells from controls and sarcoid patients expressed Fas (CD95) antigen. Although some lavage T Cells were sensitive to Fas-induced apoptosis, the viability of lavage T cells was not improved by incubation in the presence of a monoclonal antibody that inhibits Fas-induced apoptosis. Culture in the presence of interleukin 2 did prevent, at least in part, the progressive death of lavage T cells, suggesting that the viability of T cells in the lung may depend on the presence of locally delivered trophic signals. These studies emphasize that T cells on the alveolar surface are in a different state of activation and differentiation compared with that of circulating T cells, and offer a possible explanation for the impaired functional capacities observed for lavage T cells in some in vitro studies.

Adult↗
PubMed1995

Pulmonary Langerhans cell granulomatosis.

Pulmonary Langerhans cell granulomatosis (LCG), also called histiocytosis X, is characterized by the presence of destructive granulomas containing large numbers of Langerhans cells. The lesions are almost exclusively centered on distal bronchioles, and it may be more accurate to consider the disease as a bronchiolitis. Isolated pulmonary LCG is an uncommon disease that usually affects young adult smokers. Multifocal or diffuse involvement can also occur, though more often in infants or children. High-resolution computed tomography has proved to be useful in the diagnosis of the disease by allowing the identification of characteristic cystic lesions associated with nodules. Bronchoalveolar lavage strongly supports the diagnosis in only the occasional patient. The pathogenesis of pulmonary LCG remains unknown, although several arguments suggest that, at least in adults, it may result from an uncontrolled immune response initiated by Langerhans cells. Granulocyte macrophage colony-stimulating factor could be one of the factors responsible for the local accumulation of Langerhans cells in early lesions. Recently, evidence that lesional Langerhans cells are of clonal origin has been reported in patients who have various forms of the disease, but this finding has not yet been shown for pulmonary LCG. Further studies are needed to determine whether the pathogenetic mechanisms are different in patients who have localized or diffuse forms of the disease.

Adult↗
PubMed1994

[Pathogeny of sarcoidosis].

Sarcoidosis is a multisystemic granulomatous disorder due to an immune response of unknown etiology. The interactions between monocytes/macrophages and T lymphocytes through direct contact between the cells play a major role in the occurrence of these responses. Factors depending on the host, such as the polymorphism of the major histocompatibility complex molecules could be implicated in sarcoidosis pathogenesis. The factors that regulate the degree of granulomatous reaction, or those that determine the degree of fibrous response observed in some patients with sarcoidosis are poorly understood. Two recent studies, using the high sensitivity of the polymerase chain reaction, have shown the presence of M. tuberculosis DNA in 13 to 50% of biopsy samples from sarcoid patients, suggesting a role of this agent in the disease, at least in certain cases.

Antigens↗
PubMed1994

Activation of T cells by previously activated T cells. HLA-unrestricted alternative pathway that modifies their proliferative potential.

When cultured in the presence of previously activated T cells, up to 30% of resting T cells are activated, as indicated by lymphoblastic morphology, formation of cell aggregates, expression of activation Ags (CD25 and HLA-DR), and a proliferative response. This activation occurred in the absence of accessory cells and was not HLA restricted, and the TCR repertoire of the responding cells was extremely diverse without evidence for preferential expansion of T cells expressing certain V beta families or clonal populations. The ability of activated T cells to stimulate resting T cells was a transient phenomenon, which was first detected 24 h after activation and which peaked between 48 and 96 h; the stimulation of previously resting T cells produced more lymphostimulatory activity than restimulation of recently activated cells. Both resting CD4+ and CD8+ T cells expressing TCR-alpha beta and -gamma delta responded to previously activated cells, including cells with both the naive and memory phenotypes. When T cells were activated by this pathway and recultured in the presence of Ag and accessory cells, the strong proliferative response observed at 5 to 7 days with use of fresh T cells was almost entirely absent, and this impaired Ag-induced proliferative response could not be explained by the generation of suppressor cells or the inability of these cells to respond to growth factors. These findings are compatible with the possibility that Ag-specific activation of T cells permits the subsequent Ag-independent activation of other T cells and could explain the broad TCR repertoire and impaired Ag-induced proliferation of activated T cells at sites of immune reactions.

Adult↗
PubMed1994

Pulmonary sarcoidosis with a diffuse ground glass pattern on the chest radiograph.

BACKGROUND: Several chest radiographic abnormalities have been described in pulmonary sarcoidosis, but a diffuse ground glass pattern is extremely rare. METHODS: The chest radiographs of more than 1600 patients with sarcoidosis evaluated in our service between 1976 and 1991 were reviewed to determine the prevalence of this pattern on chest radiography at presentation, and to assess the clinical characteristics of these patients. RESULTS: Ten patients (0.6%) were identified with diffuse ground glass abnormalities on the chest radiography (eight men); all had associated hilar or mediastinal adenopathy. All patients were white and nine were smokers or former smokers. Nine patients were symptomatic and six had inspiratory crackles on physical examination. As a group these patients were remarkable for the frequency and severity of physiological abnormalities and the presence of various findings typically associated with "active" disease. Nine patients were followed for more than three years. All were treated with oral corticosteroids because of significant symptoms or physiological abnormalities, or both. Symptoms and radiological abnormalities disappeared or improved in all patients, but recurred in a high proportion when steroids were tapered or discontinued. By December 1992 only three patients had been withdrawn from treatment. CONCLUSIONS: A diffuse ground glass pattern on the chest radiograph is unusual in patients with sarcoidosis and may occur more commonly in white subjects and cigarette smokers. Its presence suggests the existence of active disease of recent onset likely to require long term treatment with corticosteroids.

Acute Disease↗
PubMed1994

T cell receptor repertoire of T lymphocytes recovered from the lung and blood of patients with sarcoidosis.

We evaluated the repertoire of V beta segments used in forming the T-cell receptor of lavage and blood T lymphocytes from 11 sarcoid patients and 10 normal subjects using procedures based on quantitative polymerase chain reaction, permitting analysis of both the abundance of transcripts using each of 20 different V beta families and the diversity of the VDJC beta rearrangements within each V beta family. Blood and lung T cells from sarcoid patients had a very diverse V beta repertoire. For all V beta families but one, the abundance of the V beta transcripts fell within the mean +/- 2 SD of that observed for normal blood lymphocytes; no difference in the overall abundance was observed comparing lavage and blood T cells, and the length of VDJC beta rearrangements for a given V beta family in samples from sarcoid patients was usually quite heterogeneous. Despite the overall polyclonality, evidence for selective expansion of T cells was found, in that an increased abundance of V beta 19 transcripts was observed for sarcoid blood and/or lung T cells in eight out of 11 patients studied, and rearrangements of a single predominant length using certain (e.g., V beta 19, V beta 14), but not all, V beta families were present. Sequencing confirmed the presence of a single predominant VDJC beta rearrangement in these cases. These findings suggest that the alveolitis in sarcoidosis results from two distinct processes, a local clonal expansion of T cells associated with an apparently nonspecific accumulation of T cells with an extremely diverse V beta repertoire.

Adult↗
PubMed1994

Expression of heat shock proteins in human lung and lung cancers.

Heat shock proteins (HSP) are highly conserved molecules whose expression is induced in eukaryotic cells following a broad spectrum of environmental stresses. These proteins can also be expressed by virally transformed cells and cancer cells and are important targets for T lymphocytes. Little is known about the abundance and distribution of HSP in the normal lung, the effect of cigarette smoking on their expression, or their expression in human lung carcinomas. We have used monoclonal antibodies coupled with immunohistochemical and immunoelectrophoretic techniques to evaluate the distribution of four different HSP (HSP 90 kD, HSP 73 kD/constitutive, HSP 72 kD/inducible, and HSP 63 kD) in normal lung (n = 14) and lung cancers (n = 15). In lung tissue from nonsmokers (n = 7), bronchiolar epithelial cells were intensely positive for HSP 90 kD and HSP 72 kD/inducible and weakly reactive for HSP 63 kD. Most macrophages also expressed these HSP at low levels, but no other parenchymal or immune/inflammatory cells were positive. Cigarette smoking did not modify the distribution or the intensity of HSP in bronchiolar epithelial cells, and macrophages from smokers expressed similar or lower levels of these HSP. Tumor cells from 14 of 15 lung carcinomas expressed one or more of the HSP. Considerable heterogeneity in the expression of HSP by cells in a given tumor was observed, explained in part by differences in the differentiation of the cells. Detection of HSP by immunohistochemical and immunoelectrophoretic techniques gave similar results for HSP 72 kD/inducible and HSP 90 kD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Vitamin D metabolism by alveolar immune cells in tuberculosis: correlation with calcium metabolism and clinical manifestations.

The aim of this study was to investigate the relationship between the pulmonary vitamin D metabolism in tuberculosis and the calcium metabolism abnormalities and other clinical characteristics of the disease. The metabolism of 25-hydroxyvitamin D3 (25(OH)D3) by alveolar immune cells recovered by bronchoalveolar lavage (BAL) was evaluated in parallel to the results of calcium metabolism, 25(OH) D and 1,25 dihydroxyvitamin D (1,25(OH)2D) plasma levels and other clinical parameters obtained in 14 tuberculosis patients. Whilst predominant metabolites produced by lavage cells in patients and controls were 5(E)--and 5(Z) -19-nor-10-oxo-25(OH)D3, 1,25(OH)2D3 was produced by cells from all tuberculosis patients but not by cells from controls. Calcium metabolism abnormalities were observed in only some patients, but the production of 1,25 (OH)2D3 by lavage cells was found to correlate both with 1,25(OH)2D levels (r = 0.67) and post-load urinary calcium excretion (r = 0.59). 1,25(OH)2D3 production by lavage cells was increased in patients of black origin, and those presenting with hilar adenopathy without pulmonary infiltrates, and was correlated with the number of lymphocytes recovered by lavage (r = 0.87). We conclude that 1,25(OH)2D3 production by alveolar immune cells makes a major contribution to the abnormalities in calcium metabolism seen in tuberculosis patients, and may be partly dependent on the clinical characteristics evaluated here.

Adult↗
PubMed1993

Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.

PURPOSE: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.

Acinetobacter Infections↗
PubMed1993

Diagnosis of primary tuberculosis in children by amplification and detection of mycobacterial DNA.

Standard microbiologic techniques were compared with a rapid diagnostic method based on the amplification by polymerase chain reaction (PCR) of a fragment of the IS6110 insertion element (present in multiple copies in the Mycobacterium tuberculosis genome) for the detection of M. tuberculosis in specimens obtained from children diagnosed as having primary tuberculosis on clinical grounds. Two (n = 7) or three (n = 15) gastric aspirates were obtained from the 22 children with primary tuberculosis. All specimens were negative for mycobacteria by acid-fast staining and culture. When DNA was purified from the clinical specimens and aliquots of each sample were amplified in duplicate, 15 of 59 (25%) specimens gave at least one positive result. Increasing beyond two the number of times that samples were tested did not appreciably improve sensitivity. Testing multiple samples from the same individual increased the diagnostic yield. Thus, when three different samples from the same subject were tested two times each, two or more positive results were obtained from 9 of 15 children with primary tuberculosis but 0 of 17 control subjects. Samples from children with symptoms, recent contact with patients with active tuberculosis, vesicular tuberculin responses, or abnormal chest radiographs were more frequently positive than those from patients whose only manifestation of tuberculosis was a positive (but not vesicular) tuberculin response. Thus, M. tuberculosis DNA can be detected by PCR in gastric aspirates of many children with primary tuberculosis, despite that specimens from these patients are negative by culture. Multiple samples must be tested to optimize the diagnostic yield.

Bacteriological Techniques↗
PubMed1993

Surface phenotype of Langerhans cells and lymphocytes in granulomatous lesions from patients with pulmonary histiocytosis X.

Pulmonary histiocytosis X (HX) is a disorder characterized by the presence of granulomas in which Langerhans cells (LC) and lymphocytes are abundant. Although the pathogenesis of pulmonary HX remains unknown, an uncontrolled immune response initiated by LC, which are potent antigen-presenting cells in vitro, may play an important role. To further characterize LC and lymphocytes present in granulomas from these patients, we used immunohistochemical techniques and monoclonal antibodies to evaluate the surface phenotype and electron microscopy (EM) to seek evidence for close interactions between both cell types in these lesions. In all samples, HX granulomas contained large numbers of strongly positive CD1a cells in which typical Birbeck granules were identified by EM. The number of Birbeck granules in LC from HX granulomas was strikingly increased compared with that in LC in the bronchioles of normal subjects. Furthermore, unlike normal LC, essentially all LC in HX granulomas expressed CD4 antigens and were strongly positive for CD1c. Lymphocytes infiltrating HX granulomas were almost entirely CD3+ T cells and were mainly CD4 positive (CD4/CD8 ratio 3.7 +/- 1.3). These T lymphocytes expressed almost exclusively alpha/beta T cell receptors, and gamma/delta T cells were rarely observed (< 5% of CD3+ cells). In areas of lymphocytic infiltration, close differentiated contacts between LC and lymphocytes were observed by EM in all samples. These results demonstrate that interactions between activated LC and CD4+ T lymphocytes are prominent in early HX granulomas and support the idea that an immune response in which LC serve as accessory cells is involved in the pathogenesis of this disorder.

Adult↗
PubMed1993

Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.

GM-CSF has been shown to be important for the survival and function of cells of dendritic cell/Langerhans cell (LC) lineage in vitro. Since these cells have been demonstrated to infiltrate human lung and some lung carcinomas, we hypothesized that the production of GM-CSF in the lung could be important in their recruitment and differentiation. Using both immunohistochemistry and in situ hybridization, we have shown that: (a) GM-CSF was produced by normal bronchiolar epithelium, the only site were CD1a+ LC are observed in the normal lung, whereas neither GM-CSF production nor LC were identified in normal alveolar epithelium. (b) In inflamed pulmonary tissue, hyperplastic alveolar cells produced GM-CSF, and CD1a+ LC accumulated adjacent to these cells. (c) Some, but not all, lung carcinomas produced this cytokine, and a close correlation was found between the production of GM-CSF and the number of CD1a+ LC infiltrating these tumors. Since GM-CSF was produced at all sites where CD1a+ LC are known to accumulate, but not at other locations within the lung, these data suggest that the local production of GM-CSF by certain lung cells may play an important role in determining the distribution and differentiated state of dendritic cell/LC in the human lung.

Adenocarcinoma↗