Papers by Donald McDonald
Methods for immunohistochemistry, sectioning, and flow cytometry
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Science, 2018
Zippering of cellular junctions in intestinal lacteals prevents fat uptake
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Oncotarget, 2017
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The American journal of pathology, Jan 5, 2015
Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angi... more Remodeling of blood vessels and lymphatics are prominent features of sustained inflammation. Angiopoietin-2 (Ang2)/Tie2 receptor signaling and tumor necrosis factor-α (TNF)/TNF receptor signaling are known to contribute to these changes in airway inflammation after Mycoplasma pulmonis infection in mice. We determined whether Ang2 and TNF are both essential for the remodeling on blood vessels and lymphatics, and thereby influence the actions of one another. Their respective contributions to the initial stage of vascular remodeling and sprouting lymphangiogenesis were examined by comparing the effects of function-blocking antibodies to Ang2 or TNF, given individually or together during the first week after infection. As indices of efficacy, vascular enlargement, endothelial leakiness, venular marker expression, pericyte changes, and lymphatic vessel sprouting were assessed. Inhibition of Ang2 or TNF alone reduced the remodeling of blood vessels and lymphatics, but inhibition of both t...
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The FASEB Journal, 2012
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Proceedings of the National Academy of Sciences, 1994
Substance P (SP) can cause plasma leakage at sites of inflammation by binding to neurokinin type ... more Substance P (SP) can cause plasma leakage at sites of inflammation by binding to neurokinin type 1 (NK1) receptors on the surface of endothelial cells. Internalization after ligand binding could reduce the number of NK1 receptors on the cell surface and thus participate in the desensitization and resensitization of the inflammatory response to SP. By using an antibody to the receptor, we directly observed SP-induced internalization of NK1 receptors into endosomes in endothelial cells of postcapillary venules in the rat tracheal mucosa. In the absence of SP, an average of 15 immunoreactive endosomes were present per endothelial cell. After an intravenous injection of SP, the number of immunoreactive endosomes peaked at 107 per cell at 3 min and gradually returned to the baseline by 120 min. In parallel experiments we observed that when cultured cells transfected with the NK1 receptor were exposed to rhodamine-SP and an antibody to an extracellular Flag epitope of the NK1 receptor, th...
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Proceedings of the National Academy of Sciences, 1999
In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endotheli... more In the present paper, we characterize an antibody, mAb BV13, directed to mouse vascular endothelial (VE)-cadherin, a major adhesive protein of interendothelial adherens junctions. When added to cultured endothelial cells, BV13 induces a redistribution of VE-cadherin from intercellular junctions. VE-cadherin redistribution did not change the localization of platelet endothelial cell adhesion molecule or tight junction markers such as zonula occludens 1, cingulin, and junctional adhesion molecule. Intravenous administration of mAb BV13 induced a concentration- and time-dependent increase in vascular permeability in heart and lungs. By electron microscopy, interstitial edema and accumulation of mixed types of inflammatory cells in heart and lungs were observed. Injection of (rhodamine-labeled)Ricinus communisI lectin showed focal spots of exposed basement membrane in the alveolar capillaries and in some larger pulmonary vessels. These data indicate that VE-cadherin is required for vasc...
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Proceedings of the National Academy of Sciences, 2010
Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mec... more Neutrophil chemotaxis plays an essential role in innate immunity, but the underlying cellular mechanism is still not fully characterized. Here, using a small-molecule functional screening, we identified NADPH oxidase–dependent reactive oxygen species as key regulators of neutrophil chemotactic migration. Neutrophils with pharmacologically inhibited oxidase, or isolated from chronic granulomatous disease (CGD) patients and mice, formed more frequent multiple pseudopodia and lost their directionality as they migrated up a chemoattractant concentration gradient. Knocking down NADPH oxidase in differentiated neutrophil-like HL60 cells also led to defective chemotaxis. Consistent with the in vitro results, adoptively transferred CGD murine neutrophils showed impaired in vivo recruitment to sites of inflammation. Together, these results present a physiological role for reactive oxygen species in regulating neutrophil functions and shed light on the pathogenesis of CGD.
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Neuroscience Letters, 1985
Iodinated wheat germ agglutinin (WGA) was taken up and transported by rat abducens motoneurons to... more Iodinated wheat germ agglutinin (WGA) was taken up and transported by rat abducens motoneurons to nerve terminals in the lateral rectus muscle. Five days after intracisternal injection of lectin, axon terminals wee found to be the most radioactive source, based on the density of labeling. In axons the radioactive label was concentrated in an annular region about 1.26 microns wide beneath the plasma membrane. We hypothesize that the WGA was associated with smooth vesicular and tubular structures in the axoplasm but not limited to organelles immediately beneath the axon plasma membrane. No evidence of intercellular transfer to muscle cells was found.
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Nature Biotechnology, 1999
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Journal of Histochemistry & Cytochemistry, 1988
Mast cell populations can be distinguished by differences in the content and substrate specificit... more Mast cell populations can be distinguished by differences in the content and substrate specificity of their two major cytoplasmic granule proteases, the chymases and the tryptases. To explore the origins of differences in the types of proteases present in mast cells, we used a double cytochemical staining technique to reveal both chymase and tryptase in cells from four lines of dog mast cell tumors containing both enzymes. We expected that if chymase and tryptase were expressed together during cell development the relative staining intensity of chymase compared to tryptase would be constant among different cells of each tumor. Instead, we found substantial variation in the relative intensity of chymase and tryptase staining among cells of a given mastocytoma line, each of which contained cells presumed to be monoclonal in origin but heterogeneous with respect to cell development. The overall staining intensity for chymase or tryptase correlated with the amount of protease activity i...
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Journal of Clinical Investigation, 1990
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Journal of Clinical Investigation, 1991
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Journal of Clinical Investigation, 1991
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Experimental Dermatology, 2007
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Contrast Media & Molecular Imaging, 2009
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Clinical and Translational Oncology, 2011
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Clinical & Experimental Allergy, 1994
SummaryThe endogenous tachykinins exhibit a range of properties which may he relevant in the path... more SummaryThe endogenous tachykinins exhibit a range of properties which may he relevant in the pathophysiology of asthma. Their effects on the airways seem to be modulated by a variety of lung peptidases, including neutral endopeptidase (NEP). In order to evaluate the potential role of endogenous NEP activity in modulating tachykinins‐induced bronchconstriction in man in vivo, six atopic asthmatic patients, with a mean FEV1 value of 3.38 ± 0.76 1, and a histamine PD20 mean value of 0.024 mg. were studied. The influence of inhaled phosphoramidon (a potent NEP inhibitor) was examined against the NKA‐induced bronchospasm in a double‐blind, placebo‐controlled randomized study. Changes in airway calibre were followed as FEV1 and agonists responsiveness expressed as PD20 and PD15 for histamine and NKA respectively. Patients received nebulized phospharamidon sodium salt (10−5 M) or a control solution 10 min prior to the bronchoprovocation test with NKA. No significant difference was noticed ...
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Cancer Cell, 2010
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Anatomy and Embryology, 1989
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Papers by Donald McDonald