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Biomedical subjects

J W Ryan

Publications and source records attributed to J W Ryan.

At least 91 records · Page 5Linked to original sources
PubMed1984

The ultrastructural basis of endothelial cell surface functions.

Several enzymes, enzyme inhibitors, receptors and transport structures are situated on the luminal surface of endothelium. Some enzymes and transport systems are continuously active and, in effect, regulate the composition of blood moving downstream. Other components are latent. Their activities are not expressed in the absence of stimulus. Thus, endothelial cells injured by granulocytes or viral infection possess receptors for the Fc segment of IgG and for C3b, whereas normal endothelial cells do not. Both normal and injured endothelial cells express receptors for Clq. To visualize surface enzymes, inhibitors, receptors and transport structures, we have prepared surface replicas suitable for high resolution EM. The surface replication technique, coupled with immunocytochemical procedures, facilitates studies of the topographies of surface enzymes such as angiotensin converting enzyme (ACE) and carboxypeptidase N (CPN). In addition, the replicas provide unique views of the glycocalyx, a cell coating previously believed to be amorphous but now seen to be a highly organized carpet-work under which surface enzymes, receptors, etc are embedded. Given its content of fibronectin, the glycocalyx may be the Clq receptor. Cells treated with antibodies to ACE or CPN show disarrayed glycocalyces and bind Fc and C3b. Latency of the Fc and C3b receptors may be owing to the physical barrier provided by the glycocalyx. Apparently, damage to the glycocalyx creates conditions favoring binding of immune complexes, complement activation and intravascular coagulation with loss of gradients between blood and parenchyma. Whether some non-thrombogenic properties of endothelium require an intact glycocalyx deserves consideration as does the role of the glycocalyx in regulating microvascular permeability.

Animals↗
PubMed1984

Cell biology of pulmonary endothelium.

Since the late 1960s, understanding of the cell biology of endothelium has been transformed. Endothelium is not merely a metabolically inert, semipermeable barrier separating blood from parenchyma; rather, it is a layer of metabolically active cells. In lungs, even gas exchange may be assisted by reactions occurring on the endothelial surface. Endothelial cells synthesize specific proteins (some for export); these cells have receptors and enzymes capable of reacting with certain hormones and other excitatory substances as they pass in circulating blood. Endothelium is antithrombogenic unless injured; when injured, endothelium becomes thrombogenic and then thrombolytic. Endothelium may sometimes retard the development of inflammation and at other times may facilitate it. In addition to providing sites for exchange of nutrients and metabolites, endothelium interacts with prohormones and hormones to determine the composition of blood moving downstream. The latter is a key function of pulmonary endothelium: its venous effluent is systemic arterial blood. Efforts to understand how endothelium accomplishes its wide range of metabolic activities have motivated parallel efforts to define the fine structure of the endothelial cell. Thus it has become feasible to visualize habitats of two surface enzymes, angiotensin-converting enzyme and carboxypeptidase N. Efforts to visualize surface enzymes required development of means of replicating cell surfaces, a methodology that in turn provided the first en face view of the glycocalyx. Given the ubiquity of vascular endothelium and its activities, it is difficult to imagine an area of medical practice that can safely ignore requirements for appropriately functioning endothelium.

Cardiology↗
PubMed1983

Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Studies with lower homologs and calcium antagonists.

Bovine pulmonary artery endothelial cells, in serum-free culture medium, release small quantities of prostacyclin and thromboxane A2 (3-10 and 0.1-0.3 ng/ml; measured as immunoreactive 6-ketoprostaglandin F1 alpha and thromboxane B2, respectively). The release of these substances is stimulated by up to 20-fold during a 3 min incubation with the vasodilator, bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9). Endothelial cells incubated with [3H]arachidonic acid for 24 h and then exposed to bradykinin for 3 min release 3H into the medium, approximately 65% of which co-chromatographs with 6-ketoprostaglandin F1 alpha and 3% with thromboxane B2. The effects of bradykinin are dose-related and are often discernible when the hormone is used at concentrations believed to occur physiologically (10 pg/ml; approximately 10 pM). Furthermore, the bradykinin molecule must be intact: none of its lower homologs affects the release of prostacyclin, thromboxane A2, or 3H unless used at concentrations (1 microM or higher) unlikely to be achieved in vivo. The release appears to involve calcium uptake and calmodulin: it is abolished by EGTA (5 mM) and inhibited by the 'slow channel' calcium antagonists, verapamil and nifedipine (10-100 microM), and by the calmodulin inhibitor, trifluoperazine (3-30 microM). Our findings suggest that bradykinin exerts some of its hormonal effects by acting on specific receptors possessed by vascular endothelial cells; receptor activation is associated with calcium transport, arachidonate mobilization, and a selective synthesis of prostacyclin, a vasodilator in its own right.

Animals↗
PubMed1983

Endothelial cells and inflammation.

Recent studies have brought remarkable progress in the understanding of cellular, subcellular, and molecular mechanisms of endothelial injury and responses to injury, both of which appear to be integral parts of the acute inflammatory response. The possible roles of endothelial surface enzymes in the inflammatory response are explored.

Acute Disease↗