Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the possible involvement of T-lymphocytes in the immunopathogenesis of idiopathic eosinophilic pneumonia (IEP), we have evaluated the phenotypic characteristics both of peripheral blood and alveolar lymphocytes in six patients with symptomatic IEP, and in 24 healthy nonsmokers as controls, by employing bronchoalveolar lavage (BAL), monoclonal antibodies, and flow-cytometry. In IEP, total and differential cell counts showed a mild alveolitis with an increase of eosinophil percentage and number; the alveolar lymphocyte count was also increased. In BAL, the total number both of CD4+ and CD8+ lymphocytes was significantly raised; CD4+ cells expressed early (CD25) activation antigens. The analysis of CD45R0, CD45RA and CD62L coexpression in IEP patients, when compared to healthy controls, revealed an accumulation of alveolar CD4+ cells showing phenotypic repertoire usually expressed by memory T-cells (CD45R0+, CD45RA-, CD62L-). CD8+ alveolar lymphocytes did not show any significant increase of activation antigen coexpression. Circulating lymphocytes were not significantly increased and showed only a significantly higher CD25 expression. These data suggest that a pivotal role is played by activated and memory CD4+ alveolar lymphocytes in IEP patients.
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PMID:Activated and memory alveolar T-lymphocytes in idiopathic eosinophilic pneumonia. 748 91

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
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PMID:Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. 792 34

The activation antigen, CD69, has been shown to be expressed on activated lymphocytes. CD69 has also been shown to be associated with the signal transduction process. Recently, we demonstrated the expression of CD69 on lung eosinophils obtained from the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia. In this study, we performed flowcytometric analysis of CD69 expression on eosinophils obtained from the bronchoalveolar lavage fluid, pleural effusion or peripheral blood of various patients. Whatever the disease, local eosinophils expressed significant levels of CD69, whereas most peripheral blood eosinophils did not express CD69. These findings suggest that CD69 is a marker for local eosinophils and that local eosinophils may differ functionally from peripheral blood eosinophils.
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PMID:[Expression of activation antigen, CD69, on human local eosinophils]. 803 Dec 51

Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of eosinophils in the alveolar spaces and the interstitium of the lung, frequently accompanied by peripheral eosinophilia. To clarify the roles of adhesion molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we analysed their expression by eosinophil and T-lymphocyte populations in peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11 patients with eosinophilic pneumonia, using flow cytometric methods. Cell differentials in BALF showed increased numbers of eosinophils, the increase correlating with the number of activated T-lymphocytes in BALF. The expressions of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18, CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by eosinophils in BALF were all lower than those of eosinophils in peripheral blood. In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by eosinophils in BALF, but not by those in peripheral blood. These results indicate that intercellular adhesion molecule-1 expression by eosinophils in bronchoalveolar lavage fluid but not in peripheral blood may be induced by locally activated T-cells or macrophages and may be important in the pathogenesis of idiopathic eosinophilic pneumonia.
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PMID:Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia. 898 Sep 49

Because the mechanisms of lymphocyte accumulation in the lungs of children with AIDS-associated lymphocytic interstitial pneumonia (LIP) are unknown, we studied the relative contributions of known adhesion pathways in mediating lymphocyte adherence to endothelium and the potential role of human herpesviruses in the expansion of these lesions. LIP was characterized by lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and infiltration of the pulmonary interstitium with CD8(+) T lymphocytes. In some individuals there was expansion of the alveolar septae with dense aggregates of B lymphocytes, many containing the Epstein-Barr viral (EBV) genome. Patients with concurrent EBV infection also demonstrated large-vessel arteriopathy characterized by thickening of the intimae with collagen and smooth muscle. Venular endothelium from the lung of children with LIP, but not uninflamed lung from other children with AIDS or lung from children with nonspecific pneumonitis, expressed high levels of vascular cell adhesion molecule-1 (VCAM-1) protein. In turn, inflammatory cells expressing very late activation antigen-4 (VLA-4), the leukocyte ligand for VCAM-1, were the predominant perivascular infiltrate associated with vessels expressing VCAM-1. Expression of other endothelial adhesion molecules, including intracellular adhesion molecule-1 and E-selectin, was not uniformly associated with LIP. Using a tissue adhesion assay combined with immunohistochemistry for VCAM-1, we show that CD8(+) T cell clones that express VLA-4 bind preferentially to pulmonary vessels in sites of LIP: vessels that expressed high levels of VCAM-1. When tissues and cells were pretreated with antibodies to VCAM-1 or VLA-4, respectively, adhesion was inhibited by >/=80%. Thus, infiltration of alveolar septae with CD8(+) T cells was highly correlative with VCAM-1/VLA-4 adhesive interactions, and focal expansion of B cells was coincidental to co-infection with EBV.
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PMID:Pediatric AIDS-associated lymphocytic interstitial pneumonia and pulmonary arterio-occlusive disease: role of VCAM-1/VLA-4 adhesion pathway and human herpesviruses. 2088 64

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). Evidence in vitro has implicated uPAR as a modulator of beta2 integrin function, particularly CR3 (CD11b/CD18, Mac-1). Pseudomonas aeruginosa infection has been demonstrated to recruit neutrophils to the pulmonary parenchyma by a beta2 integrin-dependent mechanism. We demonstrate that mice deficient in uPAR (uPAR-/-) have profoundly diminished neutrophil recruitment in response to P. aeruginosa pneumonia compared with wild-type (WT) mice. The requirement for uPAR in neutrophil recruitment is independent of the serine protease uPA, as neutrophil recruitment in uPA-/- mice is indistinguishable from recruitment in WT mice. uPAR-/- mice have impaired clearance of P. aeruginosa compared with WT mice, as demonstrated by CFU and comparative histology. WT mice have diminished neutrophil recruitment to the lung when an anti-CD11b mAb is given before inoculation with the pathogen, while recruitment of uPAR-/- neutrophils is unaffected. We conclude that uPAR is required for the recruitment of neutrophils to the lung in response to P. aeruginosa pneumonia and that this requirement is independent of uPA. Further, we show that uPAR and CR3 act by a common mechanism during neutrophil recruitment to the lung in response to P. aeruginosa. This is the first report of a requirement for uPAR during cellular recruitment in vivo against a clinically relevant pathogen.
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PMID:Urokinase receptor-deficient mice have impaired neutrophil recruitment in response to pulmonary Pseudomonas aeruginosa infection. 1090 58

Urokinase-type plasminogen activator (uPA) and its receptor uPAR are components of the fibrinolytic system and are important for an adequate immune response to respiratory tract infection, in part through their role in the migration of inflammatory cells. PA inhibitor-1 (PAI-1) is the predominant inhibitor of soluble and receptor-bound uPA. To determine the role of PAI-1 in host defense against pneumococcal pneumonia, the following studies were performed: (1) Patients with unilateral community-acquired pneumonia demonstrated elevated PAI-1 concentrations together with decreased PA activity in bronchoalveolar lavage fluid (BALF) obtained from the infected, but not from the contralateral, site. (2) Mice with Streptococcus pneumoniae pneumonia displayed elevated PAI-1 protein and mRNA levels in their lungs. (3) PAI-1 gene-deficient mice, however, had an unaltered immune response to pneumococcal pneumonia, as measured by cell recruitment into lungs, bacterial outgrowth, and survival. Furthermore, plasminogen-gene-deficient mice also had an unremarkable defense against pneumococcal pneumonia. These data indicate that pneumonia is associated with inhibition of the fibrinolytic system at the site of the infection secondary to increased production of PAI-1; an intact fibrinolytic response is not required for an adequate host response to respiratory tract infection, however, suggesting that the previously described role of uPA and uPAR are restricted to their function in cell migration.
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PMID:Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia. 1270 2

Leukocytes express both urokinase-type plasminogen activator (uPA) and the urokinase receptor (uPAR, CD87). We have shown that neutrophil recruitment to the lung during P. aeruginosa pneumonia is impaired in uPAR-deficient (uPAR-/-) mice but is normal in uPA-/- mice. However, both uPA-/- mice and uPAR-/- mice have impaired lung clearance of P. aeruginosa compared with wild-type (WT) mice. To determine the role of uPA and uPAR in antibacterial host defense, we compared neutrophil bacterial-phagocytosis, respiratory burst, and degranulation among uPA-/-, uPAR-/-, and WT mice. Neutrophil phagocytosis was significantly diminished comparing uPA-/- and uPAR-/- mice with WT mice at all time points. The generation of superoxide by both uPA-/- and uPAR-/- neutrophils was about half of that seen in WT neutrophils. Degranulation of azurophilic granules was significantly diminished in uPA-/- neutrophils compared with either uPAR-/- or WT neutrophils. By contrast, agonist-stimulated release of specific granules was not diminished in either uPA-/- or uPAR-/- mice compared with WT. We conclude that the uPA/uPAR system modulates several of the crucial steps in neutrophil activation that result in bacterial killing and effective innate host defense.
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PMID:Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro. 1524 Jul 45

Urokinase receptor (urokinase-type plasminogen activator receptor [uPAR], CD87), a GPI-anchored protein, is considered to play an important role in inflammation and fibrinolysis. The Gram-negative bacterium Burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in Southeast Asia. In this study, we investigated the expression and function of uPAR both in patients with septic melioidosis and in a murine model of experimental melioidosis. uPAR mRNA and surface expression was increased in patients with septic melioidosis in/on both peripheral blood monocytes and granulocytes as well as in the pulmonary compartment during experimental pneumonia-derived melioidosis in mice. uPAR-deficient mice intranasally infected with B. pseudomallei showed an enhanced growth and dissemination of B. pseudomallei when compared with wild-type mice, corresponding with increased pulmonary and hepatic inflammation. uPAR knockout mice demonstrated significantly reduced neutrophil migration toward the pulmonary compartment after inoculation with B. pseudomallei. Further in vitro experiments showed that uPAR-deficient macrophages and granulocytes display a markedly impaired phagocytosis of B. pseudomallei. Additional studies showed that uPAR deficiency did not influence hemostatic and fibrinolytic responses during severe melioidosis. These data suggest that uPAR is crucially involved in the host defense against sepsis caused by B. pseudomallei by facilitating the migration of neutrophils toward the primary site of infection and subsequently facilitating the phagocytosis of B. pseudomallei.
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PMID:Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis. 2014 64

Although pneumonia is one of the most important health problems in children, there is still no widely accepted disease severity score, the data on the correlation between the conventional inflammatory markers or chest X-ray and the disease severity remain disputable, and thus, there is an urgent need for a new pneumonia biomarker. The soluble urokinase plasminogen activator (suPAR) is a soluble form of the urokinase plasminogen activator that plays an important role in the innate host defense in the pulmonary tissue. suPAR levels have been associated with a general activation of the immune system rather than with a particular etiological factor. suPAR has a high prognostic value in critically ill patients, especially with sepsis, but there is a growing number of studies focusing on suPAR in respiratory diseases. The aim of this review is to summarize the knowledge on the role of the suPAR/uPAR in lung pathology and its possible use in pneumonia in children.
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PMID:The role of the soluble urokinase plasminogen activator (suPAR) in children with pneumonia. 2560 15


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