Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human pleural macrophages (PLM) have been studied in effusions, but little is known about normal human PLM. We therefore analyzed resting human PLM recovered by lavage before lobe resection from patients with a central bronchial tumor, not involving the pleura, and from patients with pulmonary chondroma, intrapulmonary hemorrhage, and pneumothorax. Analysis of surface antigens, phagocytosis capacity, and cytokine production was done in comparison to the regular CD14(++) blood monocytes and the recently described blood monocyte subset CD14(+)CD16(+) monocytes. When defining fluorescence intensity for the various markers on CD14(++) monocytes as 100%, the PLM gave the following pattern: CD14, 45%; CD32, 200%; CD64, 72%; CD11b, 128%; CD33, 74%; CD54, 299%; and HLA-DR, 1,906%. When CD16 on the CD14(+)CD16(+) monocytes was set as 100%, the level of CD16 expression on PLM was 7.7%. Taken together, when compared to blood monocytes, PLM appear to represent a cell-type intermediate of regular CD14(++) monocytes and the CD14(+)CD16(+) subset. In functional studies, we demonstrate that PLM can perform efficient Fc-receptor-mediated phagocytosis of antibody-coated sheep red blood cells. Compared with blood monocytes, the capacity of PLM to produce tumor necrosis factor is similar, but a striking finding in PLM was the constitutive interleukin-10 messenger RNA expression that could not be substantially increased by lipopolysaccharide stimulation. This first characterization of normal, noneffusion human PLM can form the basis for a better interpretation of findings in malignant and inflammatory exudates.
Am J Respir Cell Mol Biol 2000 Sep
PMID:Immunologic characterization of normal human pleural macrophages. 1097 Aug 35

ABSTRACT Macrophage inflammatory protein-1alpha (MIP-1alpha) is a C-C chemokine which has antiproliferative effects on early hematopoietic progenitors and stimulatory effects on later progenitors. It also possesses chemotactic and activating properties for monocytes, macrophages, and T-cells. CD34+ progenitors isolated utilizing an avidin-biotin immunoadsorption column produced significant amounts of MIP-1alpha from 24 h onward when cultured in medium with 10% fetal calf serum (>200 pg/ml). Such production persisted through 96 h of culture and was greater when such progenitors were cocultured with a preformed marrow stromal layer (4000 pg/ml at 24 h). The production of MIP-1alpha declined over time of coculture with stromal layers, and stromal layers themselves produced minimal MIP-1alpha as detected by ELISA: <100 pg/ml. In contrast, CD34+ cells isolated by flow cytometry or by magnetic bead adsorption produced minimal MIP-1alpha (0-30 pg/ml). MIP-1alpha production also increased when cells isolated by these two methods were cocultured with stromal layers. The difference in MIP-1alpha production could not be accounted for by differences in purity of the CD34+ population between isolation methods nor on the basis of monocytic or lymphocytic contamination as assessed by the presence of CD14 or CD3 positive cells. CD34+ cells isolated by immune adsorption had increased expression of endothelial and mesenchymal associated antigens, however, suggesting that this subpopulation might account for the MIP-1alpha production observed. Freshly isolated CD34+ cells expressed MIP-1alpha message as assessed by RT-PCR and by in situ hybridization. Coculture of CD34+ cells isolated by any means with stromal cells increased transforming growth factor-beta (TGF-beta) production, in this case by the stromal layer itself. Both MIP-1alpha and TGF-beta have been found to influence cell cycle status and proliferation status of early hematopoietic progenitors, and both have potential effects on accessory cell function. These studies indicate that progenitor-stromal cell interactions may influence local cytokine output, thus potentially influencing progenitor cycling status and accessory cell activation. The method of isolation of CD34+ progenitors may influence secretion of certain cytokines and chemokines.
Blood Cells Mol Dis 2000 Aug
PMID:MIP-1alpha and TGF-beta production in CD34+ progenitor-stromal cell coculture systems: effects of progenitor isolation method and cell-cell contact. 1104 27

There has been considerable interest in the effect that gram-negative bacterial endotoxin (lipopolysaccharide [LPS]) can have in asthma, given that inhalation of LPS has been shown to cause bronchial hyperresponsiveness. Further, there is evidence that the endotoxin-binding protein CD14 may be a marker for asthma. Inhaled LPS has been shown to cause an influx of eosinophils into the nasal airway and to increase the survival of CD16-negatively selected eosinophils in vitro. In this study, we compared survival of eosinophils isolated via CD16-negative selection with eosinophils that were isolated using both CD16- and CD14-negative selection criteria. Survival of CD16-negatively selected eosinophils was enhanced by LPS in a dose-dependent manner and was inhibited by the endotoxin antagonists polymyxin B or lipid X. In contrast, depletion of CD14(+) cells within the eosinophil preparations (CD14/CD16-negatively selected eosinophils) decreased the effect of LPS on survival. Preincubation of CD16-negatively selected eosinophils with antibody 60bd, which blocks LPS binding to CD14, prevented the survival-enhancing effect of LPS. However, CD14 was not detected on eosinophils by flow cytometry, even after incubation with LPS for up to 24 h. These results suggest that the survival-enhancing effect of LPS on eosinophils requires the presence of CD14(+) cells in the population. It is our hypothesis that enhanced eosinophil survival with LPS involves the contribution of another cell type.
Am J Respir Cell Mol Biol 2000 Dec
PMID:CD14(+) cells are necessary for increased survival of eosinophils in response to lipopolysaccharide. 1110 31

Anecdotal literature reports and the authors' own observations suggest an association between chromosome 8 aneuploidy and leukemia cutis. The authors investigated this potential association by using fluorescence in situ hybridization (FISH) directly on skin infiltrates in a series of 11 patients with acute monocytic leukemia (AML). Seven of the 11 patients were aneuploid for chromosome 8 by FISH which was confirmed by dual color hybridization. Six of these seven patients were AML-M4 or M5 and one was M1. The majority of the cases with leukemia cutis expressed CD4 (90% of cases), CD14 (60%), and/or CD56 (50%) in bone marrow leukemic cells. The data show the utility of examination of skin infiltrates by FISH for the detection of trisomy 8 in leukemia cutis. They also suggest the importance of trisomy 8 as a factor in predisposition to skin infiltration in AML.
Diagn Mol Pathol 2000 Dec
PMID:Increased incidence of trisomy 8 in acute myeloid leukemia with skin infiltration (leukemia cutis). 1112 42

The evaluation of monocytes recruited into the alveolar space under both physiological and inflammatory conditions is hampered by difficulties in discriminating these cells from resident alveolar macrophages (rAMs). Using the intravenous injected fluorescent dye PKH26, which accumulated in rAMs without labeling blood leukocytes, we developed a technique that permits the identification, isolation, and functional analysis of monocytes recruited into lung alveoli of mice. Alveolar deposition of murine JE, the homologue of human monocyte chemoattractant protein (MCP)-1 (JE/MCP-1), in mice provoked an alveolar influx of monocytes that were recovered by bronchoalveolar lavage and separated from PKH26-stained rAMs by flow cytometry. Alveolar recruited monocytes showed a blood monocytic phenotype as assessed by cell surface expression of F4/80, CD11a, CD11b, CD18, CD49d, and CD62L. In contrast, CD14 was markedly upregulated on alveolar recruited monocytes together with increased tumor necrosis factor-alpha message, discriminating this monocyte population from peripheral blood monocytes and rAMs. Thus monocytes recruited into the alveolar air space of mice in response to JE/MCP-1 keep phenotypic features of blood monocytes but upregulate CD14 and are "primed" for enhanced responsiveness to endotoxin with increased cytokine expression.
Am J Physiol Lung Cell Mol Physiol 2001 Jan
PMID:Monocytes recruited into the alveolar air space of mice show a monocytic phenotype but upregulate CD14. 1113 95

Little is known about the functional capabilities of bronchial macrophages (BMs) and their relationship to airway disease such as asthma. We hypothesize that BMs from asthmatics may be modulated in their function compared with similar cells from healthy individuals. BMs obtained by induced sputum from mild asthmatics (n = 20) and healthy individuals (n = 20) were analyzed using flow cytometry for CD16, CD64, CD11b, CD14, and human leukocyte antigen-DR expression, phagocytosis of IgG opsonized yeast, and oxidant production. Asthma status was assessed by lung function [percent predicted forced vital capacity and forced expiratory volume in 1 s (FEV(1))], percent sputum eosinophils, and nonspecific airway responsiveness [provocative concentration that produces a 20% fall in FEV(1) (PC(20,FEV1))]. Asthmatics with >5% airway eosinophils (AEo+) had decreased BM CD64 expression and phagocytosis compared with asthmatics with <5% eosinophils (AEo-). Among asthmatics, a significant correlation was found between CD64 expression and BM phagocytosis (R = 0.7, P < 0.009). Phagocytosis was also correlated with PC(20,FEV1) (R = 0.6, P < 0.007), lung function (%predicted FEV(1), R = 0.7, P < 0.002) and percent eosinophils (R = -0.6, P < 0.01). In conclusion, BM from asthmatics are functionally modulated, possibly by Th2 cytokines involved in asthma pathology.
Am J Physiol Lung Cell Mol Physiol 2001 Feb
PMID:Association between airway hyperreactivity and bronchial macrophage dysfunction in individuals with mild asthma. 1115 17

Fimbriae target bacteria to different mucosal surfaces and enhance the inflammatory response at these sites. Inflammation may be triggered by the fimbriae themselves or by fimbriae-dependent delivery of other host activating molecules such as lipopolysaccharide (LPS). Although LPS activates systemic inflammation through the CD14 and Toll-like receptor 4 (TLR4) pathways, mechanisms of epithelial cell activation by LPS are not well understood. These cells lack CD14 receptors and are unresponsive to pure LPS, but fimbriated Escherichia coli overcome this refractoriness and trigger epithelial cytokine responses. We now show that type 1 fimbriae can present an LPS- and TLR4-dependent signal to the CD14-negative epithelial cells. Human uroepithelial cells were shown to express TLR4, and type 1 fimbriated E. coli strains triggered an LPS-dependent response in those cells. A similar LPS- and fimbriae-dependent response was observed in the urinary tract of TLR4-proficient mice, but not in TLR4-defective mice. The moderate inflammatory response in the TLR4-defective mice was fimbriae dependent but LPS independent. The results demonstrate that type 1 fimbriae present LPS to CD14-negative cells and that the TLR4 genotype determines this response despite the absence of CD14 on the target cells. The results illustrate how the host "sees" LPS and other microbial products not as purified molecules but as complexes, and that fimbriae determine the molecular context in which LPS is presented to host cells.
Mol Microbiol 2001 Feb
PMID:Type 1 fimbriae deliver an LPS- and TLR4-dependent activation signal to CD14-negative cells. 1116 97

Inflammation plays a key role in susceptibility to coronary atherosclerosis and response to therapy. A diverse array of factors modulates inflammation, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and CD14 receptors on the surface of macrophages. Genes encoding for inflammatory markers have variants that regulate their expression and are potential risk factors for atherosclerosis. We prospectively analyzed the possible association of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C variants, located in the promoter regions, with the severity, progression, and response to therapy of coronary atherosclerosis in a well-characterized cohort. We studied 375 subjects enrolled in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping. Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. Distributions of genotypes were--for CD14: 100 CC, 184 CT, and 86 TT; IL-6: 152 GG, 153 GC, and 62 CC; and TNF-alpha: 244 GG, 110 GA, and 17 AA. The CD14 CC genotype was associated with incidence of new coronary occlusion (P=0.026); TNF-alpha AA genotype with history of myocardial infarction (MI, P=0.04), and A allele with total occlusions at baseline (P=0.027), and systolic blood pressure (P=0.046); and IL-6-174 CC genotype with baseline minimum lumen diameter (P=0.043) and reduction in lipoprotein(a) with fluvastatin (P=0.03). Otherwise, no association between the genotypes and the biochemical, angiographic, and clinical phenotypes was detected, and neither were genotype-treatment interactions. Functional variants of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C, implicated in the susceptibility to infection, are unlikely to confer major risk for susceptibility to coronary atherosclerosis and its progression or response to therapy in the LCAS population.
J Mol Med (Berl) 2000
PMID:A prospective study of genetic markers of susceptibility to infection and inflammation, and the severity, progression, and regression of coronary atherosclerosis and its response to therapy. 1119 26

Alveolar macrophages are essential for the maintenance of surfactant homeostasis. We asked whether surfactant treatment would change alveolar macrophage number and whether the alveolar macrophage phenotype would become activated or apoptotic when challenged in vivo with exogenous surfactant. Surfactant pool size in mice was increased by repetitive surfactant treatments containing 120 mg/kg (110 micromol/kg) saturated phosphatidylcholine. The number of alveolar macrophages recovered by alveolar lavage decreased after the first dose by 49% and slightly increased after the second and third doses. Up to 28.5% of the macrophages became large and foamy, and their appearance normalized within 12 h. Surfactant treatment did not increase the percent of apoptotic or necrotic cells. The alveolar macrophages were not activated as indicated by no change in expression of CD14, CD16, CD54, CD95, and scavenger receptor class A types I and II after surfactant treatment. Surfactant treatment in healthy mice transiently changed the phenotype of alveolar macrophages to large and foamy without indications of changes in the surface markers characteristic of activation.
Am J Physiol Lung Cell Mol Physiol 2001 Apr
PMID:Exogenous surfactant changes the phenotype of alveolar macrophages in mice. 1123 9

Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors.
Mol Microbiol 2001 Apr
PMID:Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. 1129 74


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