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R Robert Schellenberg

Publications and source records attributed to R Robert Schellenberg.

4 recordsLinked to original sources
PubMed2002

Interleukin-3, but not granulocyte-macrophage colony-stimulating factor and interleukin-5, inhibits apoptosis of human basophils through phosphatidylinositol 3-kinase: requirement of NF-kappaB-dependent and -independent pathways.

Basophils are key effector cells of allergic reactions. Although proinflammatory cytokines, such as interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5, inhibit eosinophil apoptosis in vitro, little is known about basophil apoptosis, and the signalling mechanisms required for basophil survival remain undefined. To address this issue, we used a novel negative-selection system to isolate human basophils to a purity of > 95%, and evaluated apoptosis by morphology using light and transmission electron microscopy, and by annexin-V binding and propidium iodide incorporation using flow cytometry. In this study, we demonstrated that the spontaneous rate of apoptotic basophils was higher than that of eosinophils as, at 24 hr, 57.6 +/- 4.7% of basophils underwent apoptosis compared with 39.5 +/- 3.8% of eosinophils. In addition, basophil cell death was significantly inhibited when cultured with IL-3 for 48 hr (84.6 +/- 4.9% vehicle-treated cells versus 40.9 +/- 3.9% IL-3-treated cells). IL-3 also up-regulated basophil CD69 surface expression. The effects of IL-3 on apoptosis and CD69 surface expression of human basophils were completely blocked by LY294002 (LY), a potent inhibitor of phosphatidylinositol 3-kinase (PI3-K), but only partially inhibited by lactacystin, a proteasome inhibitor that prevents degradation of IkappaB and NF-kappaB translocation. These observations reveal the novel finding that IL-3 prevents basophil apoptosis through the activation of PI3-K, which is only partially NF-kappaB dependent. As basophils are active participants in allergic reactions and IL-3 is one of the abundant proinflammatory cytokines in secretions from allergic tissue, we suggest that IL-3-mediated inhibition of basophil apoptosis may exacerbate the inflammation associated with allergic disorders.

Antigens, CD↗
PubMed2002

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species.

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus approximately 60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only approximately 12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (approximately 22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to approximately 9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.

Animals↗
PubMed1999

Leukemia inhibitory factor (LIF) and LIF receptor in human lung. Distribution and regulation of LIF release.

The distribution and regulation of leukemia inhibitory factor (LIF) and its receptor (LIFR) in human lung tissue is unknown. We recently found that LIF was immunolocalized to several cell types in human airways, and that exogenous LIF modulated neural and contractile responses of explanted airways. The present study aimed to determine the cellular distribution and regulation of gene transcripts for LIF and LIFR in human lung, and measured the release of LIF in response to anti-immunoglobulin (Ig)E, interleukin (IL)-1beta, and IL-6. Exposure of human lung to IL-1beta (100 pg/ml) resulted in the rapid induction of LIF messenger RNA (mRNA) (1 h) and subsequent protein release (6 h). Similar results were observed when lung tissue was exposed to anti-IgE (6 U/ml). Gene transcripts for LIF were observed in nine pulmonary cell types, with the greatest expression occurring in fibroblasts. LIFR transcripts were also widely expressed in these cell types. In cultures of nontransformed epithelial cells, lung fibroblasts, and airway smooth-muscle cells, IL-1beta (100 pg/ml) induced the rapid accumulation of LIF mRNA and protein release, with fibroblasts liberating the greatest amount. IL-6 also induced the expression of LIF mRNA and release of LIF in airway smooth-muscle cells, whereas exogenous LIF itself had no effect. Expression of LIFR mRNA was not influenced by exposure to IL-1beta or LIF in any of the cell lines used. These results highlight the widespread distribution and rapid release of LIF in human lung tissue and, in conjunction with our previous report, suggest that this cytokine may play an important role in lung inflammatory processes and neuroimmune interactions.

Bronchi↗