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C Hubeau

Publications and source records attributed to C Hubeau.

7 recordsLinked to original sources
PubMed2001

Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa.

Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous DeltaF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0.001). The number of T lymphocytes was higher at the CF distal level (P = 0.035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0.033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.

Adult↗
PubMed2001

Distinct pattern of immune cell population in the lung of human fetuses with cystic fibrosis.

BACKGROUND: Airway inflammation and infection are early events in cystic fibrosis (CF) pathogenesis. The existence of an imbalance in the immune cell population of the CF fetal airway before infection remains completely unknown. OBJECTIVE: The aim of this study was to determine whether early signs of inflammation are observed in CF airways during human fetal development. METHODS: Tracheas and lungs were collected from 21 CF and 16 non-CF fetuses. In tissue sections, the numbers of neutrophils, mast cells, macrophages, and B and T lymphocytes were quantitatively analyzed by means of image cytometry. The presence of IL-4, IL-6, IL-8, IL-10, RANTES, IFN-gamma, TNF-alpha, and NF kappa B and its inhibitor I kappa B-alpha was qualitatively evaluated by immunofluorescent staining. RESULTS: During fetal airway development, epithelial and glandular differentiation, as well as the distribution of inflammatory markers, was similar in CF and non-CF tissues. Significant differences between CF and non-CF fetal airways were observed only in the numbers of mast cells and macrophages. In the CF trachea, the mast cell number increased slowly but continuously, whereas in the non-CF trachea this number rapidly reached a plateau. In the CF lung, the macrophage number increased with time, whereas in the non-CF lung it decreased. CONCLUSION: Although no intrinsic inflammation was demonstrated, we observed a distinct appearance of mast cells and macrophages in CF airways in comparison with non-CF airways during fetal development. These 2 cell populations were greater in CF airways at a late stage of fetal development, suggesting their possible involvement in the early onset of inflammation in CF infants.

Antigens, CD↗
PubMed2000

Inflammation and infection in naive human cystic fibrosis airway grafts.

Exacerbated inflammation is now recognized as an important component of cystic fibrosis (CF) airway disease. Whether inflammation is part of the basic defect in CF or a response to persistent infection remains controversial. We addressed this question using human fetal tracheal grafts in severe combined immunodeficient mice. This model yields histologically mature, and most importantly, naive CF and non-CF surrogate airways. Significant inflammatory imbalance was found in naive CF airway grafts, including a highly increased intraluminal interleukin 8 content (CF: 10.1 +/- 2.2 ng/ml; non-CF: 1.2 +/- 0.6 ng/ml; P < 0.05) and consistent accumulation of leukocytes in the subepithelial region (P < 0.001). CF airway grafts were not histologically affected until challenged with Pseudomonas aeruginosa, which provoked: (1) early (before 3 h) and massive leukocyte transepithelial migration, (2) intense epithelial exfoliation, and (3) rapid progression of bacteria toward the lamina propria. In non-CF grafts, these three sets of events were not observed before 6 h. Using a model of naive human airways, we thus demonstrate that before any infection, CF airways are in a proinflammatory state. After infection, the basal inflammatory imbalance contributes to exert severe damage to the mucosa, paving the way for bacterial colonization and subsequent steps of CF airway disease.

Animals↗
PubMed1998

Signaling through the tetraspanin CD82 triggers its association with the cytoskeleton leading to sustained morphological changes and T cell activation.

In this report, we provide new evidence of a crosstalk between T cell activation and adhesion processes through a functional cytokeleton. We show that CD82 signaling induces long-lasting adhesion, spreading and development of membrane extensions, involving actin polymerization. Addition of various co-stimuli (phorbol 12-myristate 13-acetate or monoclonal antibodies to CD3 or CD2) increases the CD82-induced morphological alterations and, reciprocally, CD82 engagement synergizes with these stimuli to induce T cell activation as indicated by both primary tyrosine phosphorylation and IL-2 production. Different kinases are involved in both processes. CD82 co-signaling involves src kinases including p56 Ick. On the other hand, the CD82-induced alterations of cell morphology are negatively regulated by cAMP-dependent kinases independently of activation of src kinases. Simultaneously with cytoskeletal rearrangements, we observed an inducible association of CD82 with the cytoskeletal matrix. In addition, the potentiating and stabilizing effects induced by CD82 cross-linking on tyrosine phosphorylation were abolished by cytoskeleton-disrupting agents. These results suggest that the actin polymerization triggered by CD82, through its ability to associate with the cytoskeletal matrix, is the primary step involved in the CD82 induced co-stimulatory activity. Our data provide further evidence for a direct role of the actin cytoskeleton as a major component for sustained signal transduction in T cells and suggest that tetraspanins could be "membrane organizers" connecting both surface and intracellular molecules.

Antigens, CD↗
PubMed1986

Ultrastructural localization of brain 'vitamin D-dependent' calcium binding proteins.

Rat brain vitamin D-dependent calcium-binding protein (D-CaBP) was assessed for vitamin D dependency, calcium binding and ultrastructural localization within neurons. No evidence of vitamin D dependency could be derived from the experiments on vitamin D-deficient rats. A 95% pure extract of the 27-kDa brain D-CaBP was shown to bind 45Ca on nitrocellulose membrane after sodium dodecyl sulphate-electrophoresis, specifically on the 27-kDa CaBP band. Immunogold staining with electron microscopy allowed detection of D-CaBP into Purkinje cells and climbing fibers of the cerebellum. The immunoreactivity was found to be hyaloplasmic and never membrane-bound. It was present in neuronal soma, neurites and postsynaptic as well as presynaptic terminals. These findings rule out D-CaBP as a possible neurotransmitter and bring further support to the hypothesis that the protein functions as a cytosolic calcium buffer. Immunohistochemical detection of D-CaBP is proposed as a means for morphologic detection of neurons with high calcium metabolism.

Animals↗