Leukocyte Membrane Determinants Regulating Immune Reactivity is a result of the Leukocyte Culture Conference meeting held at Amsterdam in 1975. Abstracts presented in the meeting are compiled in this book. The topics of these abstracts are all under leukocyte biology and include not just lymphocytes but also monocytes, macrophages, and granulocytes. The text is composed of six major sections. The first section features abstracts that deal with ligand binding and subsequent changes in membrane. Section II focuses on the receptors on lymphocytes in the context of various subpopulations. Immune reactivity, specifically its augmentation or suppression, is the main topic of Section III. Gene products are emphasized in Section IV, while effector functions of membrane determinants are tackled in Section V. Finally, Section VI features leukocyte membrane determinants in differentiation and maturation. The book presents much detailed information that will be of great help to students or professionals in the study of biology, specifically leukocyte biology.
CONTROL OF THE LATERAL MOBILITY OF MEMBRANE PROTEINS
J.M. Oliver, H.H. Yin and R.D. Berlin, Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06032
Publisher Summary
This chapter presents studies on the mechanism by which one subcellular structure, cytoplasmic microtubule (MT) may interact with membranes to regulate surface topography. The degree of MT assembly and MT–membrane interaction in intact cells varies in a dynamic manner, depending on binding events occurring at the surface. The degree of assembly of MT and extent of MT–membrane interactions appears to be enhanced after ligand or particle binding with surface receptors. This enhancement may be mediated in part via the stimulation of cyclic GMP generation, which seems to increase MT stability. The mobility of proteins in cell membranes is regulated at least in part by MT. An intermediate step, the generation of cyclic GMP may follow ligand or particle binding and determine the stability of MT and/or of MT–membrane interaction. The immobilization of leukocyte membranes by phenylglyoxal is unrelated to changes in lipid fluidity. An arginine-rich intramembranous protein (or proteins) is involved in determining the mobility of proteins in leukocyte membranes and in controlling the deformability of the whole membrane. Although proteins are mobile in cell membranes, it is clear that they do not always diffuse at random in the lipid matrix of the membrane but rather are subject to considerable restraints on mobility.
INTRODUCTION
Characteristic changes in cell surface organization are induced by exposure of leukocytes to exogenous agents such as lectins, antibodies and phagocytic particles. These topographical changes very likely provide an initial signal for the cellular responses (metabolic stimulation, induction of cellular proliferation, etc.) that typically follow ligand binding. Thus, it is of particular importance to understand the molecular mechanisms that control the distribution and mobility of surface components.
In this paper we review our studies on the mechanism by which one subcellular structure, the cytoplasmic microtubule (MT) may interact with membranes to regulate surface topography. We also report on a new agent that can immobilize leukocyte membranes by interaction with a membrane protein. This agent is unlikely to act directly on subcellular structures such as MT or microfilaments (MF).
The Role of MT in Membrane Organization.
There is considerable evidence for a role of cytoplasmic MT in regulation of leukocyte surface topography. These data come from our studies with polymorphonuclear leukocytes (PMN) and Edelman’s studies with lymphocytes. Most of the experiments have been reviewed (1,2) and so can simply be summarized here.
First, we have observed a segregative movement of surface proteins during phagocytic ingestion of polyvinyltoluene (PVT) particles or BSA-coated oil droplets in PMN. Transport proteins are selectively excluded from areas of the membrane that are internalized while glycoprotein receptors for two plant lectins, Concanavalin A (Con A) and Ricinus communis agglutinin (RCA) are concentrated in the membrane that is internalized during phagocytosis. Recent experiments by Berlin and Fera (3) indicate that this segregative movement also occurs with membrane lipids. They determined the viscosity of membranes isolated from PMN before and after phagocytosis from fluorescence polarization studies with two lipophilic probes, perylene and 1,6-diphenyl-1,3,5-hexatriene (DPH). Their results show a dramatic reduction in plasma membrane viscosity during phagocytosis. This suggests a selective removal or “freezing out” of lipids composed of more saturated fatty acids from the membrane and retention of lipids with a less saturated fatty acid composition.
These specific changes in surface organization appear to be regulated by MT. Pretreatment of cells with colchicine, which does not interfere with the phagocytic process per se but inhibits MT assembly abolishes the directed movement of membrane components. Thus, in colchicine-treated cells, transport proteins, lectin receptors and membrane lipids are all internalized at random during phagocytosis.
MT also appear to regulate the distribution and lateral mobility of receptors for ligands such as plant lectins and antibodies in leukocyte membranes. For example, when PMN from normal black (C57/6J) mice are labelled with fluorescein isothiocyanate-conjugated Con A (F-Con A), the majority of cells show an essentially random distribution of bound lectin. (Table 1, line 1, Fig. 1a). When these cells are pretreated with 10−6M colchicine for 30 minutes there is a large increase in the numbers of cells that form surface caps with Con A and a corresponding decrease in random labelling (see Table 1, line 2; Fig. 1c). Similarly, Edelman and coworkers (4) showed that lymphocytes form caps when labelled with small amounts of F-Con A (less than 5 μg/ml) but not at higher doses. However, in the presence of colchicine, capping was observed on cells labelled with both low and high concentrations of lectin.
TABLE I
THE DISTRIBUTION OF F-CON A ON MOUSE PMN
Figure 1 The distribution of F-Con A on mouse PMN. a) Normal PMN, diffuse labelling predominates; b) CH PMN, most cells are capped; c) normal PMN treated with colchicine (10−6M, 30 minutes), most cells are capped; d) CH PMN treated with cyclic GMP (0.5 × 10−4M, 30 minutes), labelling is diffuse. Initial magnification × 1000. For details see ref. 9.
Thus, colchicine-sensitive structures, presumably MT, appear to restrict the mobility of lectin-receptor complexes in leukocyte membranes. Disruption of MT releases these constraints and permits the complexes to move into large aggregates or caps.
Control of MT Assembly and Membrane-MT Interaction.
Recent evidence indicates that the degree of MT assembly and MT-membrane interaction in intact cells varies in a dynamic manner, depending on binding events occurring at the surface. For example, morphological studies by Reaven and Axline (5) have shown MT and MF closely associated with areas of macrophage membranes in contact with a glass surface or a phagocytic particle and absent from resting areas of the membrane, and Weissmann and coworkers (6) have demonstrated increases in the numbers of MT profiles in human PMN after brief exposure to zymosan particles or the C5a component of complement. Edelman’s capping study, in which low doses of F-Con A formed surface caps but higher doses did not, suggests that a critical amount of this particular ligand must bind before MT assembly and receptor immobilization occur.
Studies in our laboratory suggest an intermediate step between a binding event at the cell surface and MT assembly: generation of cyclic GMP. This occurs presumably via activation of a membrane-associated guanyl cyclase. This hypothesis arose from studies of F-Con A binding to peripheral blood PMN from the C57/6J beige mouse, a spontaneous mutant of the C57/6J black mouse (7) and a homologue of the Chediak-Higashi (CH) syndrome of man (8). Unlike normal mouse PMN which do not cap except after colchicine treatment, CH PMN cap spontaneously with F-Con A (compare Tables I and II, lines 1 and 2; Fig. 1, a, b, c). That is, they behave like cells lacking intact MT (9).
TABLE II
Monolayers of peripheral blood PMN were labelled with F-Con A (5 μg/ml, 10–15 minutes) as previously described (9) and the distribution of bound lectin observed by fluorescence microscopy. Random, a uniform ring of fluorescence. Capped, fluorescence concentrated in a polar shell or knob. Patched, fluorescence in patchy distribution inside the cell as a result of internalization of lectin-receptor complexes.
It is possible to reduce cap formation in CH PMN to normal levels by pretreatment of the cells with a number of different agents (Table 2). The active drugs include cyclic GMP (line 3, Fig. 1d) two analogues of acetylcholine (carbamylcholine or carbachol and carbamyl β-methyl choline or bethanechol) (lines 4 and 5) and the cocarcinogen phorbol myristate acetate (PMA) (line 7). The latter compounds stimulate cyclic GMP generation in PMN (10). The cholinergic agents appear to act via a muscarinic receptor since their activity is inhibited by atropine (lines 7 and 8). The effect is chemically specific for cyclic GMP and cannot be reproduced with guanine, guanosine or 5′GMP. Cyclic AMP and prostaglandin E1(PGE1), that stimulates cyclic AMP generation in PMN, are also ineffective at reducing Con A cap formation.
These active agents have no direct effect on cap formation in normal black mouse PMN. However, they antagonize the increased capping that follows colchicine treatment in normal PMN (Table 1), indicating that they also enhance MT stability in normal cells.
Other agents that inhibit Con A capping on CH cells include two gastrointestinal secretory hormones that have been reported to elevate cyclic GMP levels in their target cells (11). The first and most...
| Erscheint lt. Verlag | 2.12.2012 |
|---|---|
| Sprache | englisch |
| Themenwelt | Sachbuch/Ratgeber ► Natur / Technik ► Naturführer |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| Technik | |
| ISBN-10 | 0-323-14247-8 / 0323142478 |
| ISBN-13 | 978-0-323-14247-2 / 9780323142472 |
| Haben Sie eine Frage zum Produkt? |
PDF (Adobe DRM)Größe: 74,3 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
EPUB (Adobe DRM)Größe: 8,9 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
aus dem Bereich
