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Biomedical subjects

P J Edelson

Publications and source records attributed to P J Edelson.

At least 55 records · Page 3Linked to original sources
PubMed1978

Plasma membrane localization and metabolism of alkaline phosphodiesterase I in mouse peritoneal macrophages.

Alkaline phosphodiesterase I activity is demonstrable in lysates of mouse resident peritoneal macrophages (1.43 mU/mg), endotoxin-stimulated macrophages (1.36 mU/mg), and thioglycollate-stimulated macrophages (3.91 mU/mg), as well as in the lysates of several mouse cell lines. The enzyme showed little variation in culture, although serum deprivation caused a 50% decrease in enzyme activity. In each of the three macrophage types about 80% of the enzyme is inactivated by the diazonium salt of sulfanilic acid, indicating that this enzyme is a component of the plasma membrane. In thioglycollate-stimulated cells about the same fraction of enzyme can be inactivated with papain corroborating this assignment. The enzyme is inactivated with a half-time of 14.1 h in resident cells, but this is decreased to 8.2 h in endotoxin cells, and to 5.7 h in thioglycollate cells. These results are consistent with the hypothesis that the endogenous pinocytic rate is a major determinant of plasma membrane turnover. In addition, the different synthetic rates measured in resident and inflammatory cells support the concept that macrophage activation is a differentiative process leading to a qualitatively new cell type.

Animals↗
PubMed1978

Biochemical and functional characteristics of the plasma membrane of macrophages from BCG-infected mice.

A set of quantitative signs of activation, previously developed in studies of inflammatory peritoneal macrophages, has been applied to the study of immunologically stimulated peritoneal cells. Mice that are infected systemically with Bacillus Calmette Guérin (BCG) and then challenged locally with soluble mycobacterial antigens generate populations of cells that spread rapidly in culture, display an elevated pinocytic rate, ingest IgMC-coated sheep erythrocytes, and have diminished levels of 5'-nucleotidase activity. These effects depend on sensitization with live organisms, require secondary antigenic challenge, and develop on the same schedule as does effective cell-mediated immunity. The challenge is antigen specific and cannot be replaced by a nonspecific inflammatory stimulus. Thus, the characteristics of inflammatory macrophages that were previously defined are applicable to the study of immunologically mediated macrophage activation. Cells sharing this pattern of characteristics, whatever their mode of generation, are proposed to represent a distinct class of differentiated macrophages, as compared with the resident macrophage population.

Animals↗
PubMed1977

Distribution of concanavalin A in fibroblasts: direct endocytosis versus surface capping.

Indirect immunofluorescence of intact or acetone-extracted cells has allowed us to distinguish concanavalin A (Con A) which is associated with the plasma membrane of CHO cells from Con A which has been interiorized. We find that Con A is directly endocytized by these cells with no intervening stage of plasma membrane aggregation. The lectin accumulations observed by direct fluorescence are actually cytoplasmic collections of pinosomes which contain Con A. Only in a small fraction of CHO cells are true plasma membrane aggregates, or caps, found. This predominance of direct pinocytic interiorization over capping was not affected by dibutyryl cAMP or by treatments which can disrupt microtubules, including cold shock or exposure of the cells to anti-mitotic agents. Cytochalasin B, however, inhibited the uptake of Con A and at the same time promoted the formation of large surface aggregates of the lectin, or minicaps. Capping may reflect a competition between aggregation in the plane of the membrane and direct interiorization of bound lectin. Surface cap formation may be a characteristic process of cells with very low endocytic rates, such as lymphocytes.

Binding Sites↗
PubMed1976

5'-Nucleotidase activity of mouse peritoneal macrophages. I. Synthesis and degradation in resident and inflammatory populations.

Mouse resident peritoneal macrophages display sufficient 5'-nucleotidase activity to hydrolyze 58 nm AMP/min per cell protein. This activity increases approximately 163 nm AMP/min per mg after 72 h in culture. The enzyme is renewed in unstimulated cells with a half-time of 13.9 h. The activity is not reduced by treatment of intact cells with a variety of proteolytic enzymes, including trypsin, pronase, urokinase, and plasmin. Cells obtained from an inflammatory exudate have diminished or absent levels of enzyme activity. Endotoxin-elicited cells display enzyme activitiy of 20.9 nm AMP/min per mg, while thioglycollate-stimulated macrophages have no detectable activity. The reduced level of activity in endotoxin-stimulated cells is due to their elevated rate of enzyme degradation, with a half-time of 6.9 h. Their rate of enzyme synthesis is essentially normal. No evidence for latent enzyme activity could be obtained in thioglycollate-stimulated cells, nor do these cells produce any inhibition of normal cell enzyme activity. Serum deprivation reduces the enzyme activity of resident cells to about 45% of control activity. These conditions do not significantly affect the rate of enzyme synthesis, but again are explainable by an increase in the rate of enzyme degradation. Pinocytic rate is elevated in endotoxin-stimulated cells which show a more rapid rate of enzyme degradation than unstimulated cells do. However, in serum-free conditions, the rate of enzyme degradation is doubled with no change in the pinocytic rate of the cells.

Animals↗
PubMed1976

5'-Nucleotidase activity of mouse peritoneal macrophages. II. Cellular distribution and effects of endocytosis.

The diazonium salt of sulfanilic acid (DASA) can inactivate about 80% of the total 5'-nucleotidase of viable macrophages. The remaining 20% can be inactivated if the cells are first lysed in detergent, and presumably represents an intracellular pool of 5'-nucleotidase. The bulk of this pool may represent cytoplasmic vesicles derived from plasma membrane by endocytosis. This internal compartment is expanded up to threefold immediately after the cells have ingested a large latex load. This is consistent with previous observations on the internalization of 5'-nucleotidase in latex phagosomes. In latex-filled cells this intracellular pool of enzyme is inactivated over a few hours, and the cells then slowly increase their enzyme activity to nearly normal levels. However, 24 h after latex ingestion the metabolism of 5'-nucleotidase in these recovered cells is abnormal, as the rate of enzyme degradation is about twice the normal rate, and the DASA-insensitive enzyme pool in these cells is strikingly diminished. This may reflect effects of the accumulated indigestible particles on the fate of incoming pinocytic vesicles or on newly synthesized plasma membrane precursor. Another endocytic stimulus, concanavalin A, also reduces the total cell 5'-nucleotidase activity. This effect, which is time and temperature dependent, can be prevented by the competitive sugar alpha-methyl mannose. The concanavalin A inhibition can be reversed in the absence of new protein synthesis or in cells cultivated in serum-free conditions. It is not known whether the effect of concanavalin A on 5'-nucleotidase depends upon the interiorizaiton of plasma membrane or is strictly associated with events at the cell surface.

Animals↗
PubMed1975

The pinocytic rate of activated macrophages.

Peritoneal macrophages from mice injected 4 days previously with Brewer's thioglycollate medium have a pinocytic rate, in culture, of 190 ng horseradish peroxidase (HRP)/100 mug cell protein/h, compared to the rate of resident peritoneal cells of 53 ng HRP/100 mug cell protein/h. Mice injected with endotoxin or with only certain of the components of the Brewer's medium show an intermediate level of stimulation. The rate of unstimulated, endotoxin-stimulated, or thioglycollate-stimulated cells shows little change over several days in culture. The pinocytic rate of thioglycollate-stimulated cells can, however, be further increased by exposure of concanavalin A. Although cells may show transient increases in their pinocytic rate in many situations, a sustained increase in pinocytic rate is a sign of the "activated" state of macrophages.

Animals↗
PubMed1974

Effects of concanavalin A on mouse peritoneal macrophages. I. Stimulation of endocytic activity and inhibition of phago-lysosome formation.

Concanavalin A (Con A) binds to saccharide residues on the mouse peritoneal macrophage plasma membrane and stimulates extensive pinocytic interiorization of the membrane. The overall pinocytic rate is increased 3.5-4.5 times by the addition of Con A, and the surface marker enzyme adenosine triphosphatase can be identified histochemically in association with the cytoplasmic vesicles generated after exposure of the cells to Con A. Once formed, these pinocytic vesicles may persist for several days and fail to show morphologic evidence of fusion with primary or preformed secondary lysosomes. There is no apparent effect on the capacity of the macrophage to ingest either latex particles or IgG-coated SRBC administered either simultaneously with or subsequent to the Con A.

Acid Phosphatase↗
PubMed1974

Effects of concanavalin A on mouse peritoneal macrophages. II. Metabolism of endocytized proteins and reversibility of the effects by mannose.

The half-time for the degradation of horseradish peroxidase (HRP) is increased from 14 h to 37 h in Con A-treated cells, while the half-time for the degradation of [(125)I]BSA is increased from 5.4 h to 14.8 h. This supports prior microscopic observations which suggested that Con A pinosomes showed a marked impairment in their ability to form phagolysosomes. Artifacts due to anomalous behavior of HRP-Con A complexes, or to inhibition of lysosomal hydrolases by Con A, could be excluded. These indications of impaired phagolysosome formation, as well as those described in the preceding paper, could be reversed by postincubation of the cells in mannose, but not in galactose. This reversal is accompanied by a dissociation of Con A-FITC from the inner surface of the pinosome membrane, into the vesicle contents. These observations may be relevant to the ability of Con A to affect several membrane characteristics, and are also of interest in relation to the impaired formation of phagolysosomes which has been described in certain in vitro parasitic infections of macrophages or other cells.

Animals↗
PubMed1974

A renal lesion in asphyxiating thoracic dysplasia.

A boy with asphyxiating thoracic dysplasia was studied from age seven months until his death with congestive heart failure at age thirteen months. Aminoaciduria, phosphaturia, increased urate excretion, hyposthenuria, proteinuria, and metabolic acidosis were demonstrated at one year of age. Cardiopulmonary dysfunction and skeletal abnormalities were also studied during life. Cessation of linear growth, overgrowth of membranous bone with retardation of enchondral bone formation, and cartilaginous overgrowth of the chest were prominent findings. At autopsy, an unexpected hepatic fibrosis was discovered, along with renal and skeletal disorganization.

Bone and Bones↗
PubMed1973

Peroxidase-mediated mammalian cell cytotoxicity.

Lactoperoxidase, in the presence of hydrogen peroxide and iodide is cytotoxic for human and mouse lymphoid cells, and human erythrocytes. Myeloperoxidase, in amounts equivalent to 1.5 x 10(6) neutrophils, readily replaces lactoperoxidase, and allows the substitution of the iodide ion by chloride. The myeloperoxidase-mediated reaction is rapid, and highly efficient, leading to 85-90% cell death in 90 min, as measured by (51)chromium release and dye exclusion. The mixture of granulocytes. monocytes, and lymphocytes present in an inflammatory exudate, and the intimate cell-to-cell association characteristic of cytotoxic phenomena may provide the in vivo requirements for such a system.

Animals↗
PubMed1973

Effect of vinblastine on the chemotactic responsiveness of normal human neutrophils.

The effect of vinblastine on the mobility of human neutrophils was studied. Chemotactic responsiveness was decreased by approximately 80 to 95%, as measured in Boyden chambers, whereas random mobility, as measured in glass capillary tubes, was approximately doubled. Chemotactic responsiveness could be partially restored after dialysis of the treated cells, which is not compatible with an action of vinblastine on microtubules. The possibility is considered that this observation is an additional example of the effect of several microtubular binding agents on phenomena mediated at the phagocytic surface.

Cell Membrane↗
PubMed1972

Diagnosis of immunologic deficiency in childhood.

A defective host response may be responsible for recurring infections in certain children. Recognition of these defects may be important both therapeutically for the patient and for genetic counseling for the family. Family history, age of onset of illness and type of infecting agents may all point to one or another defect in host resistance. An initial evaluation for suspected immunologic disease may be rapidly accomplished and should include absolute neutrophil and lymphocyte counts, chest X-ray for a thymic shadow, Schick test for functional IgG antibodies and isohemagglutinin titers for functional IgM antibodies. Although serum protein electrophoresis is unreliable for diagnosis of most disorders of circulating antibodies, quantitation of the IgG, IgA and IgM antibody classes is generally available. More extensive studies may be carried out to further define defects in the cell-mediated immune system, in the various complement components, or in the ingestion and killing of bacteria by neutrophils.

Age Factors↗