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)

L-selectin is a glycoprotein which is one of three members in a family of cell adhesion molecules called selectins. L-selectin is present in distinct forms on both neutrophil granulocytes and lymphocytes, and it appears to play an important role in the early stages of leukocyte-endothelial cell interaction. Activation of leukocytes leads to shedding of the extracellular part of L-selectin which thus forms a soluble adhesion molecule, sL-selectin, which retains functional capacity and can be detected in serum. In the present study we have developed a specific, sensitive sandwich ELISA to measure the serum level of sL-selectin in patients with hematological and infectious disorders. Three patients with acute myeloid leukemia in remission and 1 patient with chronic myeloid leukemia in chronic phase were followed during bone marrow transplantation and the level of sL-selectin was found to correlate closely to the leukocyte counts with no detectable sL-selectin during periods of severe leukopenia. In 11 patients with chronic phase chronic myeloid leukemia and 13 patients with chronic lymphocytic leukemia the sL-selectin level was also found to correlate closely to the leukocyte count (R = 0.98; p = 0.001 and R = 0.83; p = 0.004 respectively). One CML patient with a leukocytosis of 385 x 10(9)/l was found to have an sL-selectin concentration 625 times above normal. Ten patients with acute pneumonia were evaluated at diagnosis and at the time of follow-up 4-8 weeks later. In all patients the initial sL-selectin level was higher than at follow-up. However, no close correlation between sL-selectin and leukocyte count or CRP (C-reactive protein) at the time of diagnosis was found. In summary, we have found that the sL-selectin level in human serum closely correlates to the leukocyte count in both CML and CLL and during bone marrow transplantation.
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PMID:Correlation between serum level of soluble L-selectin and leukocyte count in chronic myeloid and lymphocytic leukemia and during bone marrow transplantation. 769 Mar 31

In acute bacterial pneumonia, polymorphonuclear leukocytes (PMN) sequester in the lung and migrate into the alveolar airspaces. These local events are accompanied by a systemic response that includes release of PMN from the bone marrow into the circulation. The present study was designed to compare the sequestration and migration of these newly released PMN with those already in the circulation in a model of acute streptococcal pneumonia in rabbits. PMN were labeled in the mitotic pool in the marrow by administration of 5'-bromo-2'-deoxyuridine (BrdU 100 mg/kg) and the labeled cells were detected in blood and tissues by immunohistochemistry. The proportion of BrdU-labeled PMN (PMN BrdU) that sequestered and migrated in the lung tissue infected with Streptococcus pneumoniae and the uninfected lung was measured using morphometric techniques. The results show an increase in the proportion of PMN BrdU (6.0 +/- 1.0% to 17.3 +/- 3.8%, P<0.05) in the circulation 5 h following the induction of a pneumonia and the PMN expressed a higher concentration of L-selectin (9.3 +/- 0.7 to 14.9 +/- 0.8 MFI, P<0.05). The proportion of PMN BrdU in the control tissue was not different from the proportion in the systemic circulation (11.4 +/- 1.6%). The PMN BrdU increased in the pneumonic site at 5 h (19.9 +/- 3.4%, P<0.05) and 8 h (26.6 +/- 1.5%, P<0.05) after treatment. Only 2.8 +/- 0.3% and 2.8 +/- 0.6% of the PMN that migrated into the airspace at 5 and 8 h were PMN BrdU. We conclude that PMN released into the circulation as part of the systemic response to a local streptococcal pneumonia sequester normally but may be slow to migrate into the airspaces at the inflammatory site.
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PMID:Polymorphonuclear leukocyte (PMN) migration in streptococcal pneumonia: comparison of older PMN with those recently released from the marrow. 884 71

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

These studies tested the hypothesis that L-selectin plays a role in neutrophil traffic in the lungs, particularly in neutrophil margination, sequestration, and emigration, using L-selectin-deficient mice. No defect in neutrophil margination within either capillaries or arterioles and venules was observed in uninflamed lungs of L-selectin-deficient mice. The initial rapid sequestration of neutrophils within the pulmonary capillaries 1 min after intravascular injection of complement fragments was not prevented. In contrast, L-selectin did contribute to the prolonged neutrophil sequestration (> or = 5 min). Interestingly, neutrophil accumulation within noncapillary microvessels required L-selectin at both 1 and 5 min after complement injection. During bacterial pneumonias, L-selectin played a role in neutrophil accumulation within noncapillary microvessels in response to either Escherichia coli or Streptococcus pneumoniae and within capillaries in response to E. coli but not S. pneumoniae. However, L-selectin was not required for emigration of neutrophils or edema in response to either organism. These studies demonstrate a role for L-selectin in the prolonged sequestration of neutrophils in response to intravascular complement fragments, in the intracapillary accumulation of neutrophils during E. coli-induced pneumonia, and in the accumulation of neutrophils within noncapillary microvessels when induced by either intravascular complement fragments or
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PMID:Neutrophil margination, sequestration, and emigration in the lungs of L-selectin-deficient mice. 902 88

Considerable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe infections in non-neutropenic hosts. This beneficial effect is attributed to an enhancement of granulopoiesis and neutrophil function, the latter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. We compared neutrophil function and phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator-dependent pneumonia, at baseline and following initiation of G-CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatment compared with baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml. After correction for lavage dilution effects, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (FcgammaRI, FcgammaRII, FcgammaRIII, CR3, and L-selectin) or indicators of neutrophil function such as respiratory burst activity, phagocytosis and killing of Candida albicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortality of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression.
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PMID:Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia. 964 99

Changes in lymphocyte subsets in the trachea, pulmonary tissue, bronchoalveolar lavage (BAL), peripheral blood and bronchial lymph node (BLN) of gnotobiotic calves infected with bovine respiratory syncytial virus (BRSV) were analysed by flow cytometry. Following BRSV infection, virus titres in the nasopharynx reached a peak between days 5 and 7 and infection was resolving from day 10. Although calves did not develop signs of clinical respiratory disease, there was evidence of gross pneumonia and histological changes typical of BRSV bronchiolitis, which were most extensive from day 710 of infection. Following BRSV infection there was a recruitment of CD8+ T cells into the trachea and lung, which peaked on day 10 after infection. Thus, there were approximately equal numbers of CD8+ and CD4+ T cells in the lung and trachea of uninfected calves, whereas by day 10 of infection, CD8+ cells outnumbered CD4+ cells by 3:1 in the lungs and 6:1 in the trachea of the infected calves. Although the increase in CD4+ T cells into the lungs was less marked than that of CD8+ T cells, changes in expression of CD45R, CD45RO, L-selectin and interleukin-2 receptors all suggested that CD4+ T cells were activated during BRSV infection. Changes in gamma delta T cells were not observed in BRSV-infected calves. There was a marked increase in B cells in the BLN after infection and BLN CD4+ T cells changed from the majority expressing L-selectin and CD45R in uninfected calves to a predominance of L-selectin- CD45R- CD45RO+ phenotype, 10 days after infection. In conclusion, CD8+ T cells constitute the major lymphocyte subpopulation in the respiratory tract of calves recovering from BRSV infection.
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PMID:Phenotypic analysis of local cellular responses in calves infected with bovine respiratory syncytial virus. 1041 49

During inflammation, leukocyte emigration from the circulation can be directed by the endothelium, in part by the inducible endothelial adhesion ligand for L-selectin. In this study, endothelial L-selectin ligand expression was localized by immunohistochemistry in human lung in several different types of lung inflammation and in systemic inflammation. Endothelial L-selectin ligand was not seen in normal lung or in acute pneumonia involving neutrophil accumulation. However, the endothelial ligand was seen in most cases of chronic interstitial pneumonia with mononuclear cell accumulation (a mean of 5.9% of microvessels positive). Regarding granulomatous conditions, in sarcoidosis the endothelial ligand was not identified, but in tuberculous infection some expression was seen in a minority of cases (mean 3.3% of microvessels positive). In contrast, consistent, typically extensive ligand induction (mean 33.4% of microvessels positive) was present in bronchiectatic lung showing prominent lymphocytic accumulation and venules with thickened (high) endothelium, the latter being normally characteristic of lymphoid tissue in which L-selectin ligand is known to be constitutively expressed. Lung from subjects with systemic infection was negative for endothelial expression of the ligand. These studies show how in a defined extralymphoid tissue induction of endothelial L-selectin ligand depended not only on the presence or absence of an inflammatory state, but also on the nature of the inflammation.
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PMID:Selective induction of endothelial L-selectin ligand in human lung inflammation. 1044 62

Interstitial cytomegalovirus (CMV) pneumonia is a clinically relevant complication in recipients of bone marrow transplantation (BMT). Recent data for a model of experimental syngeneic BMT and concomitant infection of BALB/c mice with murine CMV (mCMV) have documented the persistence of tissue-resident CD8 T cells after clearance of productive infection of the lungs (J. Podlech, R. Holtappels, M.-F. Pahl-Seibert, H.-P. Steffens, and M. J. Reddehase, J. Virol. 74:7496-7507, 2000). It was proposed that these cells represent antiviral "standby" memory cells whose functional role might be to help prevent reactivation of latent virus. The pool of pulmonary CD8 T cells was composed of two subsets defined by the T-cell activation marker L-selectin (CD62L): a CD62L(hi) subset of quiescent memory cells, and a CD62L(lo) subset of recently resensitized memory-effector cells. In this study, we have continued this line of investigation by quantitating CD8 T cells specific for the three currently published antigenic peptides of mCMV: peptide YPHFMPTNL processed from the immediate-early protein IE1 (pp89), and peptides YGPSLYRRF and AYAGLFTPL, derived from the early proteins m04 (gp34) and M84 (p65), respectively. IE1-specific CD8 T cells dominated in acute-phase pulmonary infiltrates and were selectively enriched in latently infected lungs. Notably, most IE1-specific CD8 T cells were found to belong to the CD62L(lo) subset representing memory-effector cells. This finding is in accordance with the interpretation that IE1-specific CD8 T cells are frequently resensitized during latent infection of the lungs and may thus be involved in the maintenance of mCMV latency.
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PMID:Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62L(lo) memory-effector cell pool during latent murine cytomegalovirus infection of the lungs. 1109 Jan 46

Radiation pneumonitis is a distinct clinical entity that differs from other pulmonary symptoms such as allergic pneumonitis, chemical pneumonitis, or pneumonia by various infectious agents. Recent research has supported the mechanism of cellular interaction between lung parenchymal cells and circulating immune cells mediated through a variety of cytokines including proinflammatory cytokines, chemokines, adhesion molecules, and profibrotic cytokines. Identifying reliable biomarkers for radiation pneumonitis will allow us to identify individuals at risk for pneumonitis before or during the early stage of therapy. Prospective blood sampling, scoring of respiratory symptoms, and chest imaging were conducted for patients receiving thoracic radiotherapy for malignancy. Serial plasma specimens were analyzed for circulating cytokine changes before, during, and up to 12 weeks after radiation. Radiation pneumonitis was diagnosed using National Cancer Institute (NCI) common toxicity criteria. Cytokine analysis was assayed for interleukin 1alpha (IL-1alpha), interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), E-selectin, L-selectin, transforming growth factor beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) using enzyme linked immmunosorbant assay (ELISA). Twenty-four patients had clinical follow-up longer than 12 months after radiotherapy. Thirteen had symptomatic pneumonitis (NCI grade 2). The peak incidence of symptoms was between 6 and 13 weeks after radiotherapy. Six patients had only radiographic infiltrates (NCI grade 1). Five patients did not have clinical or radiographic pneumonitis. Both IL-1alpha and IL-6 levels were significantly higher before, during, and after radiotherapy for those who had pneumonitis. The pattern of changes of MCP-1, E-selectin, L-selectin, TGF-beta1, and bFGF varied, but none of these cytokines correlated with radiation pneumonitis. Analysis of a panel of circulating cytokines with different putative functions in radiation pulmonary injury identified IL-1alpha and IL-6 as early circulating cytokine markers for radiation pneumonitis.
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PMID:Radiation pneumonitis and early circulatory cytokine markers. 1191 81

ADAM (a disintegrin and metalloprotease) family members are membrane-anchored proteins with wide ranging functions, including proteolytic cleavage of cell surface molecules, cell fusion, cell adhesion and intracellular signaling. ADAM8, also known as CD156a, is expressed mainly in cells of the immune system, such as monocytes, neutrophils, eosinophils, dendritic cells, and B cells. It can cleave a variety of substrates and is a sheddase for CD23 and L-selectin. ADAM8 has an important role in allergic inflammation. ADAM8 mRNA expression is increased with disease progression in asthma. ADAM8 is strongly induced by allergens and Th2 cytokines in the lung in experimental asthma. Soluble ADAM8 is elevated in the bronchoalveolar lavage fluid of patients with eosinophilic pneumonia and has a physiologic role in protecting against allergic pulmonary disease in experimental murine asthma. Together, these findings support the view that ADAM8 might be a therapeutic target for allergic respiratory diseases. This review discusses novel strategies for immune intervention in allergic respiratory disease.
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PMID:ADAM8 in allergy. 1869 Nov 40


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