Showing papers by "Howard Hughes Medical Institute published in 1972"

Angiotensin I: metabolism by plasma membrane of lung.

Abstract: (8-L-[ 14 C] phenylalanine) angiotensin I is metabolized in one passage through blood-free lungs. Approximately 20 percent of the radioactivity emerges as angiotensin 11, the remainder as lower homologs. Radioactivity is not retained by the lungs but has the same volume of distribution and mean transit time as blue dextran, a compound unlikely to leave the intravascular space. Plasma membrane fractions of lung are capable of converting angiotensin I to angiotensin II. These data, taken together, indicate the circulating angiotensin I is metabolized by enzymes of the luminal surface of pulmonary endothelial cells.

Substructural features of pulmonary endothelial cavaolae

Abstract: Substructural specializations of the endothelial caveolae of rat lung capillaries are described. Dense knobs occur at the place where caveola membrane, diaphragm and plasma membrane fuse. Similar structures are seen where caveolae fuse to form complex groups and in preparations of isolated caveolae. The appearance of these knobs in transverse sections may represent a circular skeletal structure, possibly functioning to maintain the patency of the stoma and the integrity of the diaphragm. In addition, the inner concave surface of the caveola membrane contains regularly spaced globular structures, possibly enzyme clusters or binding sites. This interpretation is supported by the finding that the distribution of lead phosphate deposits (formed on reaction of caveolar 5'-nucleotidase with AMP in the presence of Pb(N0(3))(2)) corresponds with the spacing of globular structures. These substructural features of caveolae are considered with reference to the ability of caveolae to metabolize circulating vasoactive substances.

Pulmonary Endothelial Cells and the Metabolism of Adenine. Nucleotides, Kinins and Angiotensin I

Abstract: As indicated in previous publications (1–9) and as revealed in the preceding paper (10), it is likely that circulating adenine nucleotides, kinins and angiotensin I are metabolized by enzymes of the luminal surface of the pulmonary endothelium. One of the nucleotides, namely adenosine-5’-monophosphate (AMP), is metabolized by enzymes of caveolae intracellulares open to the vascular lumen (7–9). This enzymic activity is not peculiar to those caveolae open to the vascular lumen, as one can show by reactions performed on fixed blocks of tissue (5,6) that other caveolae and intracellular vesicles are capable of degrading nucleotides. However, in the case of metabolism of circulating nucleotides it appears that only those caveolae open to the lumen have access to the substrate.

Immediate Immunologic Reactions: Noncytolytic Mediator Release and Cytolytic Cell Destruction

Abstract: Two of the principal mechanisms by which immunologic reactions generate chemical mediators of the inflammatory response differ both in their mode of interaction with target cell membranes and in their ultimate effect on these membranes In the cytolytic reaction [Fig 1(A)] antibodies of certain immunoglobulin classes (IgM or IgG) bind to the target cell via combining sites specific for antigens which are either intrinsic to the cell membrane or have become passively bound to it A resultant configurational change in the Fc portion of the antibody (Ashman and Metzger, 1971) is associated with the initiation of a sequence of reactions among certain serum proteins, the components of complement,* contained in the surrounding milieu The physicochemical characteristics and mechanism of interaction of the nine components have recently been reviewed (Muller-Eberhard, 1968; Ruddy, et al, 1972) Chemical mediators of inflammation are generated during the complement reaction sequence per se, by the limited proteolysis of the components These mediators represent both major (eg, C3b, an enhancer of opsonization) and minor (eg, C3a, an anaphylatoxin) fragments of component cleavage as well as complexes (eg, C567, a chemotactic principle) formed by the interaction of products from different components If completion of the reaction sequence occurs on a cell membrane, cytolytic destruction of the cell results which in some instances, may eventuate in mediator release