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Biomedical subjects

C Jarstrand

Publications and source records attributed to C Jarstrand.

At least 19 recordsLinked to original sources

Macrophage reaction in rabbit lung following inhalation of iron chloride.

Groups of eight rabbits were inhalation-exposed to iron, 1.4 +/- 0.7 mg/m3 (low Fe), or 3.1 +/- 1.8 mg/m3 (high Fe) as FeCl3 or to filtered air (controls) for 2 months, 5 days/week and 6 hours/day. The alveolar macrophages were increased in number in both exposed groups. Noduli of granular macrophages were found in lungs of all the rabbits in the high-Fe group, in one from the low-Fe group, and in one control rabbit. Especially in the high-Fe group there were prominent changes in the macrophages such as enlarged lysosomes containing fibrous-looking structures, iron-rich inclusions, and densely packed, 5-nm electron-dense granules. The number of cells filled with surfactant-like inclusions as well as a smooth surface was increased in the high-Fe group and the macrophages had enhanced phagocytic capacity. There was an increase in the phospholipid concentration and in the volume density of type II cells in the high-Fe group but the level of phosphatidylcholines was not significantly changed. The fact that Fe3+ affected mainly the alveolar macrophages might be due to the relatively high concentration of iron in these cells caused by the precipitation of iron in their lysosomes.

Administration, Inhalation

Rabbit lung after combined exposure to soluble cobalt and trivalent chromium.

Eight rabbits were exposed to 0.7 +/- 0.4 mg/m3 Co2+ as CoCl2 and 1.2 +/- 0.7 mg/m3 Cr3+ as Cr(NO3)3 (group Co + Cr), eight to 0.6 +/- 0.5 mg/m3 Co2+ (group Co), and eight to filtered air (control group), for 4 months, 5 days/week, and 6 hr/day. All rabbits in group Co + Cr and group Co showed nodular aggregation of alveolar epithelial type II cells. Volume density of the type II cells was significantly higher in group Co + Cr than in group Co and the control group. There was intraalveolar macrophage accumulation in seven rabbits in group Co + Cr, one in group Co, and one in the control group. In lavage fluid the numbers of macrophages and the percentage of these cells with smooth surface and intracellular surfactant-like inclusions were more increased in group Co + Cr than in group Co as were oxidative metabolic and phagocytic activities of the macrophages. Total phospholipids, phosphatidylcholines, and especially 1,2-dipalmitoylphosphatidylcholine was markedly increased in group Co + Cr whereas only 1,2-dipalmitoylphosphatidylcholine was slightly increased in group Co. One mechanism behind the high amount of surfactant phospholipids in group Co + Cr seems to be an enhanced production of surfactant by the type II cells. Another mechanism is probably that Cr3+ reduces the capacity of alveolar macrophages to catabolize surfactant. The results imply that it is important to investigate effects of combinations of cobalt and chromium in the occupational environment.

Animals

The role of O-antigen polysaccharide in the activation of neutrophils by lipopolysaccharides of Salmonella species.

Activation of neutrophils by lipid A, O-antigen polysaccharides (PS) and smooth lipopolysaccharides (LPS) isolated from Salmonella choleraesuis (O-6,7) and Salmonella typhimurium (O-4,5,12) was investigated. The methods used were assays for lysozyme release and for nitroblue tetrazolium (NBT) reduction which measures the level of oxidative metabolism of neutrophils. LPS from both species stimulated neutrophils to the same extent in the presence of autologous plasma. In the absence of plasma only the O-6,7 LPS activated neutrophils. Lipid A or PS isolated from both LPS either did not activate neutrophils or did so only at very high concentrations when tested in the presence of plasma; in the absence of plasma no activation occurred. The data indicate that both PS and lipid A segments of LPS are required for activation of neutrophils by LPS. We also deduce that plasma, probably complement, is required for the interaction of some LPS, e.g. O-4,5,12 with neutrophils whereas other LPS, e.g. O-6,7 can interact directly and activate neutrophils.

Antigens, Bacterial

Effect of Brucella abortus lipopolysaccharide on oxidative metabolism and lysozyme release by human neutrophils.

Both Brucella abortus lipopolysaccharide (LPS) and lipid A were low activators of nitroblue tetrazolium reduction and lysozyme release in human neutrophils. The stimulation was dose dependent and was higher in the presence of autologous plasma than in its absence. The comparison between Brucella LPS and lipid A versus Salmonella LPS revealed that at least 100 times more LPS and 1,000 times more lipid A of the former genus were required to induce significant nitroblue tetrazolium reduction and a corresponding lysozyme release in neutrophils. Low Brucella LPS-mediated superoxide and lysozyme production might contribute to the survival of these facultative intracellular bacteria in phagocytic cells.

Bacterial Toxins

Alveolar macrophages and lung lesions after combined exposure to nickel, cobalt, and trivalent chromium.

In earlier inhalation exposures of rabbits, nickel increased the production of surfactant by type II cells, with secondary effects on morphology and function of alveolar macrophages. Cobalt induced mainly a nodular growth pattern of the type II cells. Trivalent chromium seemed to impair the capacity of macrophages to catabolize surfactant but did not affect the type II cells. We exposed rabbits by inhalation to combinations of nickel (0.6 mg/m3 as NiCl2) and trivalent chromium [1.2 mg/m3 as Cr(NO3)3] (Ni-Cr), cobalt (0.5 mg/m3 as CoCl2) and nickel (0.5 mg/m3) (Co-Ni), or cobalt (0.5 mg/m3) and chromium (1.2 mg/m3) (Co-Cr) for 4 months, 5 days/week, 6 hr/day. Alveolar macrophages, alveolar type II cells, and lung content of phospholipids were determined. All combined exposures induced more pronounced lung lesions than exposures for each of the metals. Phospholipid concentrations were significantly higher. There were significantly higher percentages of macrophages filled with surfactant-like inclusions and a smooth surface. Accumulations of macrophages in alveoli were more widespread. Chromium potentiated the effects of nickel and cobalt on the type II cells, which led to secondary effects on the macrophages. Nickel potentiated the specific effects of cobalt, i.e., type II cell nodule formation. The result indicates that noxious effects could also be induced in man by combined exposure to nickel, cobalt, and trivalent chromium in concentrations similar to those occurring in some occupational settings.

Animals

Intralipid decreases the bacterial lipopolysaccharide induced release of oxygen radicals and lysozyme from human neutrophils.

Human neutrophils were incubated either with purified cell envelope lipopolysaccharides (LPS) of salmonella or with different concentrations of LPS combined with Intralipid. Incubation of neutrophils with LPS alone increased their oxidative metabolism with increased release of oxygen radicals as measured by the nitroblue tetrazolium (NBT) test and chemiluminescence response. The amount of lysozyme released by the cells also increased during incubation with LPS. However, when the neutrophils were incubated with LPS together with Intralipid, the LPS induced stimulation of the neutrophil NBT reduction, chemiluminescence and lysozyme release was significantly decreased. Intralipid might substitute for plasma high density lipoproteins (HDL), which are known to inhibit the LPS effects on the neutrophils in the acute stage of an infection with Gram-negative bacteria.

Cells, Cultured

Significance of oxygen availability for release of oxygen free radicals and lysozyme by neutrophils.

Neutrophilic granulocytes were exposed to an atmosphere of nearly 100% oxygen (hyperoxia) for one hour. The nitroblue tetrazolium (NBT) reduction, reflecting oxygen radical release, was decreased both in resting and stimulated cells, but lysozyme release was unchanged. Short time exposure of patients to oxygen hypertension might therefore be beneficial as therapy, in conditions where reduced production of oxygen radicals is required. The NBT reduction of resting and stimulated neutrophils in an atmosphere of purified argon (hypoxia) was also considerably decreased, and the lysozyme release unchanged. This reflects the anaerobic conditions in abscesses, where the contribution of neutrophil oxygen metabolites to the killing of microorganism might be reduced.

Cell Hypoxia

Influence of human plasma high density lipoproteins from septic patients on different functions of normal human neutrophils.

High Density Lipoproteins (HDL) from three patients with E. coli sepsis contained high, low and no Serum Amyloid Protein (Apo SAA), respectively. Preincubation of neutrophils from healthy persons for half an hour with sepsis HDL as well as normal HDL increased the phagocytosis, the stimulated nitroblue tetrazolium reduction, the chemotaxis and the random migrations of these cells. However, for all these functions, lower values were obtained after incubation with sepsis HDL containing high amounts of apo SAA than with normal HDL. A qualitative change of HDL might thus in part be responsible for the decreased function of neutrophils noted during the acute phase of bacterial infections.

Adult

Neutrophil leucocyte function in primary hyperparathyroidism.

Neutrophil leucocyte chemotaxis, phagocytosis and oxidative metabolism were measured in six patients with primary hyperparathyroidism (HPT) who underwent parathyroidectomy. The preoperative neutrophil chemotaxis value was 6.2 +/- 0.3 arb.U. and this decreased to 5.8 +/- 0.5 arb.U. (p less than 0.05) on the third postoperative day and to 5.4 +/- 0.3 arb.U. three weeks later. Serum calcium levels were 2.95 +/- 0.06 mmol/l preoperatively and decreased to 2.20 +/- 0.05 (p less than 0.05) and 2.34 +/- 0.05 mmol/l (p less than 0.05) on the third and 21st day after parathyroidectomy. Phagocytosis measured as the intracellular uptake of complement-opsonized yeast particles by neutrophils was not influenced by operation. In a control group, six patients undergoing hemithyroid ectomy due to microfollicular tumours were studied. In this group leucocyte chemotaxis, phagocytosis and serum calcium levels were not significantly different before and after surgery. Neutrophil oxidative metabolism, measured by the ability of the cells to reduce nitroblue tetrazolium (NBT), was similar in the HPT and control groups both before and after operation. The results indicate that HPT is associated with an abnormal leucocyte migration which is reversed after successful parathyroidectomy.

Calcium

Rabbit lung after inhalation of lithium chloride.

Rabbits were exposed to aerosols of lithium chloride in metal concentrations of 0.6 and 1.9 mg/m3 (mass median aerodynamic diameter of 1 micron) for 4-8 weeks, 5 days/week, 6 h/day. The lungs were studied by light and electron microscopy, with particular reference to inflammatory changes, structure of alveolar macrophages and alveolar epithelial cells. Macrophages recovered by lung lavage were studied by light and electron microscopy and their oxidative metabolic activity was measured. The content of phospholipids was analysed in lung tissue. Exposure to lithium produced no significant effects. It thus seems that Li+ is less toxic to the lung than the other metals investigated with the same test system, e.g. Ni2+, Cd2+, Co2+, Cr3+ and Cr6+.

Administration, Inhalation

Alveolar macrophages in rabbits after combined exposure to nickel and trivalent chromium.

Rabbits were exposed to a combination of 0.7 mg/m3 Ni2+ as NiCl2 and 1.2 mg/m3 of Cr3+ as Cr(NO3)3, to 0.6 mg/m3 of Ni2+ as NiCl2, or to filtered air for about 4 months, 5 days/week and 6 hr/day. Alveolar macrophages were recovered by lung lavage and studied by light and electron microscopy. Metabolic activity, phagocytic capacity and lysozyme activity in the macrophages were studied. After the combined exposure, the effects on lung weight, number of macrophages, and appearance of surface and number of intracellular laminated inclusions in these cells were more than additive. These effects might be explained by a combination of increased production by Ni2+ and impaired catabolism of surfactant by Cr3+. Because the metal concentrations used were not far above occupational threshold limit values, combined exposures to nickel and trivalent chromium should be considered more seriously.

Animals

Increased production of malondialdehyde in patients with HIV infection.

The mean plasma content of malondialdehyde (MDA) in 30 patients in different stages of HIV infection was found to be about 30% higher than that in controls. The phenomenon was not correlated to the degree of immunodeficiency and was noted early in the course of the disease. This indicates a higher degree of basal lipid peroxidation, which might contribute to the tissue damage seen in these patients. A new reverse phase liquid chromatography method was used for quantitative measurements of MDA in plasma after reaction of this compound with thiobarbituric acid.

AIDS-Related Complex

Interferon induction and granulocyte function in patients with viral meningitis.

In 22 consecutive patients with acute viral meningitis we studied the ability of neutrophilic granulocytes to phagocytize yeast particles, the interferon (IFN) levels in serum and cerebrospinal fluid as well as the activity of the enzyme 2'-5' oligoadenylate synthetase in peripheral lymphoid cells. During the acute stage of illness a decreased phagocytosis of the neutrophils was demonstrated, while the adherence of yeast particles to the cells was increased. This was accompanied by the presence of IFN in the cerebrospinal fluid and an increase in the 2'-5' oligoadenylate synthetase activity of peripheral lymphoid cells. About two months after onset of symptoms the synthetase activity and the phagocytic activity of granulocytes were restored to normal levels. The results of this study may indicate that the impaired neutrophil function in viral disease is influenced by increases in IFN levels in vivo.

2',5'-Oligoadenylate Synthetase

Detection and semiquantitative determination of antibodies against Plasmodium falciparum in human blood serum: NBT-reduction by polymorphonuclear leukocytes.

Nitroblue tetrazolium (NBT) reduction by polymorphonuclear leukocytes (PMN) has been employed for the detection of specific opsonizing antibodies against Plasmodium falciparum in sera from individuals exposed to malaria parasites. Specific antibody-antigen complex is known to trigger the metabolic activation of normal PMN, as measured by NBT-test. In the sera from 16 out of 17 patients tested the NBT-reduction of normal PMN was, in the presence of P. falciparum antigen, significantly higher than that obtained with pooled normal serum from individuals without malaria background. This enhancement was more pronounced in the presence of complement. NBT-reduction was elevated to a lower extent when human anti-P. falciparum sera were substituted with anti-P. vivax or P. ovale sera. Furthermore, no enhancement was noted when red blood cells lysate was used as antigen. The results indicated the presence of specific opsonizing antibodies against P. falciparum in the patient sera. Oxygen-derived free radicals formed by PMN during the stimulation are suggested as the neutrophil mediated protection against malaria.

Animals

Lysozyme activity in ultrastructurally defined fractions of alveolar macrophages after inhalation exposure to nickel.

Rabbits were exposed to 0.6 mg/m3 of nickel as NiCl2 for about one month. After exposure, alveolar macrophages were lavaged from the lung and divided into three fractions by elutriation. Laminated structures in the macrophages were related to fraction number so that the fractions with the largest cells contained the highest number of structures. The lysozyme activity decreased in unfractionated as well as in fractionated macrophages from nickel exposed rabbits. The decrease was most pronounced in the fraction with the smallest macrophages and smallest number of laminated structures. Therefore the pronounced decrease in lysozyme activity seen in this and earlier studies is not caused by the increased amount of surfactant material. Increased amount of surfactant is a hallmark of nickel inhalation exposure and the surfactant material is responsible for the morphological and metabolic effects of the macrophages. The decreased lysozyme activity is probably a direct effect of nickel on the macrophages.

Animals

Morphology and function of blood monocytes after incubation with lung surfactant.

Human blood monocytes were incubated for different periods of time with lung surfactant (phospholipid concentration 1-2.5 mg/ml). After short-term (30 min) incubation, there was an increase in the nitroblue tetrazolium (NBT) reduction of the monocytes both at rest and during stimulation with E. coli bacteria, and enhanced ingestion of fluorescein-labelled yeast particles. Electron microscopic examination of the same monocytes showed an active cell surface with numerous protrusions. Long-term (24 h) incubation with surfactant resulted in a reduced ability of the cells to adhere to plastic dishes. Although the NBT-reduction of resting monocytes was increased after long-term incubation with surfactant, the additional enhancement of NBT-reduction after stimulation with bacteria was decreased. These cells were rounded, usually devoid of surface structures, their nuclei were condensed, and their cytoplasm filled with surfactant material. Thus, monocytes are initially activated in the presence of surfactant, but if the cells become overfed with surfactant lipids their functional capacity decreases.

Animals

Selenium effects on human neutrophilic granulocyte function in vitro.

The effects of an inorganic selenium salt on phagocytic functions of human neutrophilic granulocytes from donors with a low activity of glutathione peroxidase have been investigated. Granulocytes were exposed for 60 min in vitro to sodium selenite in two physiological concentrations (100 and 200 ng Se/ml) and one unphysiologically high concentration (2000 ng/ml). The spontaneous and chemotactic migration, the nitroblue tetrazolium reduction, the phagocytosis of fluorescein-labeled yeast particles and the intracellular killing of staphylococci were then studied in such granulocytes and compared to control cells, which had not been exposed to selenium. The migration and nitroblue tetrazolium reduction abilities of granulocytes were not affected by selenium exposure. The phagocytic and bactericidal activities were significantly increased in granulocytes exposed to selenium in physiological concentrations. However, at 2000 ng Se/ml these activities were found to be equal to or lower than control levels. Thus selenium supplementation might enhance phagocytic and bactericidal functions of human granulocytes, thereby improving the host defense against bacterial infections.

Bacteriolysis

Rabbit alveolar macrophages after long-term inhalation of soluble cobalt.

Rabbits were exposed to 2 or 0.4 mg/m3 of cobalt as CoCl2 for 14-16 weeks (5 days/week and 6 hr/day). More macrophages were lavaged from the lungs of rabbits exposed to the higher Co2+ concentration, and the diameter and variation of the diameter of the macrophages were significantly larger than in controls. The activity of lysozyme in the lavage fluid and in the macrophages was increased in the two exposed groups. Some macrophages in the exposed animals were large and engorged with intracellular lamellar inclusions and lipid droplets. Most of these cells had a smooth surface. The oxidative metabolic activity measured by reduction of nitroblue tetrazolium was increased in the exposed groups. The number of yeast cell particles attached to the surface of the macrophages was increased in the group exposed to the high concentration, but the number of ingested particles was not affected by cobalt exposure. Apart from the fact cobalt increased lysozyme activity whereas nickel decreased it, cobalt produced the same type of effects on macrophages as nickel did in earlier studies. Cobalt affected only a minor proportion whereas nickel affected most macrophages. This can be explained by the fact nickel produced a general increase in the volume density of the type II cells while cobalt affected the type II cells only in some areas of the lungs.

Administration, Inhalation