Biomedical subjects

A Eklund

Publications and source records attributed to A Eklund.

At least 127 records · Page 7Linked to original sources

PubMed1993

Quartz selectively down-regulates CR1 on activated human granulocytes.

We have investigated the interaction between quartz and granulocytes with respect to complement receptor expression. When N-formylmethionyl-leucyl-phenylalanine (fMLP)-stimulated leukocytes were exposed to quartz at 37 degrees C, CR1 was down-regulated but CR3 was not affected. This was a direct effect on granulocytes because it occurred in a similar fashion when mixed leukocyte suspensions and isolated granulocyte populations were used as targets for quartz. The observed down-regulation by quartz was not affected by the microfilament-disrupting agent cytochalasin B and the total detectable pool of CR1 was reduced after quartz exposure. When protease inhibitors, such as aprotinin or phenylmethanesulfonyl fluoride, were present during quartz exposure, the down-regulation of CR1 was less pronounced, but this was not the case not when protease inhibitors such as EDTA-Na2 and pepstatin were present. Exposure to quartz was not accompanied by a pronounced release of beta-glucuronidase (marker for the primary granules) or vitamin B12 binding protein (marker for the secondary granules). In contrast to quartz, exposure to alumina did not affect the expression of CR1 and CR3. The spontaneous mobilization of CR1 at 37 degrees C was reduced when quartz was present but the CR3 mobilization was unaffected. Our results indicate that quartz induces a granule protease-dependent selective shedding of CR1 but not CR3 despite a low degree of degranulation.

Aprotinin↗

PubMed1993

Terpenes enhance metabolic activity and alter expression of adhesion molecules (Mac-1 and L-selectin) on human granulocytes.

Granulocytes from healthy blood donors were exposed to terpenes dissolved in ethanol. Flow cytometry was used to measure the expression of the cell surface receptors Mac-1 L-selectin, and CR1, which were detected by monoclonal antibodies. The phagocytic activity was determined by using C3b-coated yeast particles as prey. The metabolic activity was measured by determining the intracellular hydrogen peroxide production using dichlorofluorescein diacetate. After terpene exposure the expression of Mac-1 and CR1 increased (P < 0.001 and P < 0.01, respectively) and the expression of L-selectin decreased (P < 0.001). There was also an increased metabolic activity (P < 0.001). The cell viability, the cell count, and the phagocytic activity remained unchanged. These findings suggest that terpene exposure triggers the granulocytes to a higher degree of activation in terms of an altered expression of the adhesion molecules and an increased metabolic activity.

Cell Adhesion↗

PubMed1993

Presence of serum modulates expression of complement receptor type 1 (CR1) on human granulocytes after quartz exposure.

We have investigated the interaction between granulocytes and quartz with respect to the expression of complement receptor type 1 (CR1) and the presence of normal human serum (NHS). Quartz down-regulates selectively CR1 on activated granulocytes. This down-regulation is abolished in the presence of both NHS and heat-inactivated NHS (NHS56) but not human albumin. When quartz was preincubated with NHS (quartz-NHS) before exposure to activated granulocytes, a down-regulating effect was observed in contrast to preincubation with NHS56, which did not induce a down-regulation. Preincubation with cytochalasin B reduced the down-regulation of quartz-NHS, indicating a cytoskeleton-dependent internalization of the receptor. The serine protease inhibitor PMSF partly reduced this down-regulation. Our results indicate that the presence of NHS in the alveolar space influences the interaction between quartz and recruited granulocytes with respect to CR1 expression. Since CR1 is an important opsonin receptor and soluble CR1 can modulate the inflammatory response, this may be of importance in the inflammation and fibrosing process induced by quartz in the alveolar space and lung interstitium.

Blood Physiological Phenomena↗

PubMed1993

Metabolic activity in human alveolar macrophages increases after cessation of smoking.

Alveolar macrophages (AMs) were recruited by bronchoalveolar lavage (BAL) from human smokers before and one, three, and six months after smoking cessation. The metabolic activity of the AM was quantified as luminol-enhanced chemiluminescence (CL) both at rest and after in vitro stimulation with phorbol myristate acetate (PMA). The resting CL values did not differ before and after smoking cessation. The activity after PMA stimulation was unaltered at one and three months. However, the maximal metabolic response, as well as the rate, were significantly (P < 0.02 and P < 0.01, respectively) higher at six months, compared to prior smoking cessation. In addition, the time to reach the maximal peak was reduced after six smoke-free months, indicating a more rapid cell activation. The cell concentration in the BAL-fluid decreased (P < 0.001) as soon as after one smoke-free month and remained low at the following lavages. The lower metabolic response one and three months after smoking cessation, and the increased response six months after, together with a rapid normalization of the cell concentration in the BAL fluid, may be explained by the persistence of tobacco-smoke particles in the alveolar space, which could influence cell activity.

Bronchoalveolar Lavage Fluid↗

PubMed1993

Long term effects of alumina on components of bronchoalveolar lavage fluid from rats.

Significant differences in several components of bronchoalveolar lavage fluid (BAL fluid) have previously been reported in aluminium potroom workers compared with controls. The present paper describes the long term effects in rats of one time exposure to potroom aluminium oxide without fluorides (primary alumina (PA)) or with adsorbed fluorides (secondary alumina (SA)) on components of BAL fluid. Alumina dust (40 mg) suspended in saline was instilled intratracheally; controls received saline. Bronchoalveolar lavage (BAL) was performed one, four, and 12 months after exposure. The number of cells in BAL fluid was increased significantly (p < 0.05) by SA but not PA. The increase was mainly macrophages, but the concentrations of neutrophils also increased about 10-fold one and 12 months after exposure. Although albumin and hyaluronan concentrations did not differ from those of controls, fibronectin concentrations were significantly (p < 0.001) increased one year after exposure both in PA exposed and SA exposed rats. The results indicate that SA, possibly because of adhered fluorides, induces early changes in alveolar cell populations including persistent neutrophilia. These cellular changes may have a destructive effect. The late pronounced increase of fibronectin in both PA and SA exposed rats indicates a delayed effect of alumina on the extracellular matrix.

Aluminum↗

PubMed1993

Comparison of dietary casein and soybean protein effects on plasma lipid and gastrin levels, hepatic delta 6-desaturase activity and coronary arteriosclerosis in male Sprague-Dawley rats. A 9-month study.

An increased concentration of gastrin was observed in plasma of male Sprague-Dawley strain rats fed on soybean protein diet for a 9-month period, compared with rats fed on casein diet. Both diets contained 0.5% (w/w) cholesterol. Protein-dependent differences were also observed in the fatty acid pattern of hepatic phospholipids, hepatic delta 6-desaturase activity, and plasma cholesterol. No signs of arteriosclerosis were observed in the aortas. Sixty percent of the hearts showed various degrees of lipid staining in coronary arterial branches of different sizes. Despite a large difference in plasma cholesterol level, there was no quantitative or qualitative difference between groups in the occurrence of coronary lipid staining.

Animals↗

PubMed1993

Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with sarcoidosis.

Sarcoidosis affecting the lungs may cause obstructive and/or restrictive lung function impairment. The bronchial reactivity is related to the release of histamine from the mast cells. Upon activation mast cells also release tryptase. This enzyme may activate latent collagenase and thus possibly contribute to the fibrosis formation observed in sarcoidosis. We analyzed the bronchoalveolar lavage fluid (BALF) from 13 nonsmoking and untreated patients with sarcoidosis and from 30 healthy volunteers (18 smokers) with regard to the number of mast cells and the tryptase concentration. Concomitantly albumin, fibronectin and hyaluronan were measured as markers of the inflammatory reaction in the alveoli and interstitium. The number of mast cells was higher (p < 0.001) in patients with sarcoidosis than in controls. Also, the concentration of tryptase was significantly higher in patients (225.3 +/- 83.9 [SEM] mU/L) compared to nonsmoking and smoking controls (34.7 +/- 7.8 and 44.7 +/- 13.0 mU/L, respectively; p < 0.01 for both). In addition, the concentrations of albumin, fibronectin and hyaluronan were higher in patients with sarcoidosis compared to the nonsmoking controls (p < 0.001 for all). However, there was no relationship between either the mast cell number or the tryptase concentration and the lung function parameters (VC, TLC, FEV1, FEV%, DLCO). As our patients did not show any functional signs of bronchial obstruction (FEV1 91.7% +/- 13.3 [SD] and FEV% 99.5% +/- 6.4 of predicted) the lack of correlation is not surprising. The high concentrations observed in the BALF of the noncellular components may just reflect an ongoing inflammatory process that may resolve or, if exaggerated, lead to fibrosis.

Adult↗

PubMed1993

Recurrent Löfgren's syndrome in three patients with sarcoidosis.

Löfgren's syndrome (acute onset of sarcoidosis with erythema nodosum, arthritis, sometimes fever and bilateral hilar lymphoma) is a well known clinical entity. Recurrent Löfgren's syndrome is, however, extremely rare. We report three cases of recurrent Löfgren's syndrome. The duration between the first manifestation of the syndrome and the first relapse varied between two and eight years. One of the patients had two relapses, two and six years after the initial onset of disease.

Adult↗

PubMed1993

Short-term in vivo exposure to cigarette-smoke increases the fluorescence in rat alveolar macrophages.

Alveolar macrophages (AMs) from human smokers exhibit a strong intracellular fluorescence. In order to study the mechanisms behind the fluorescence, we wanted to determine whether it could be induced by short term exposure to smoke. We therefore exposed rats for either one or five days to cigarette smoke. AMs were recovered by bronchoalveolar lavage (BAL), and their fluorescence was quantified by flow cytofluorometry. AMs from rats exposed to two cigarettes, on a single occasion, showed an increased fluorescence compared to controls. The fluorescence was further enhanced by exposing rats to two cigarettes, for five consecutive days. Larger and more granular/complex AMs were more fluorescent than smaller and less granular/complex cells. Smoke-exposed rats (five consecutive days) lavaged immediately after the exposure, had less cells in their BAL fluid than control animals. However, when rats were lavaged three smoke-free days after the exposure, the cell recovery increased, probably due to less airway obstruction. In conclusion, we found that a short-term in vivo exposure to cigarette smoke results in an increased AM fluorescence. The findings can be one explanation for the strong fluorescence seen in AMs from human smokers, possibly due to endocytosis of fluorescent material.

Animals↗

PubMed1993

Inhibitory effect of gastrin and cholecystokinin fragments on the secretion of triacylglycerol in rat hepatocytes.

In this investigation we studied the influence of two gastrin fragments, pentagastrin and nonsulfated heptadecagastrin, and two cholecystokinin fragments, sulfated and desulfated cholecystokinin 26-33, on intracellular and secreted triacylglycerol in isolated hepatocyte cultures. Both gastrin fragments inhibited triacylglycerol release in a biphasic manner, exhibiting maximal effect at 0.1 nmol/L (nonsulfated heptadecagastrin) and 0.3 nmol/L (pentagastrin). At these concentrations triacylglycerol secretion was 42% (nonsulfated heptadecagastrin, p < 0.001) and 62% (pentagastrin, p < 0.001) lower than in cells untreated with gastrin. Sulfated cholecystokinin 26-33 caused a 35% decrease in triacylglycerol secretion at 0.1 nmol/L (p < 0.01), and desulfated cholecystokinin 26-33 caused a 53% decrease at 0.2 nmol/L (p < 0.001). In all experiments, the hormone-induced decrease in triacylglycerol secretion was accompanied by an increase in intracellular triacylglycerol content. The cholecystokinin-A receptor antagonist L-364, 718 did not affect the decrease in triacylglycerol secretion induced by 0.3 nmol/L pentagastrin, whereas the cholecystokinin-B receptor antagonist L-365, 260 inhibited the pentagastrin effect at concentrations above 50 nmol/L. These results suggest that gastrin, cholecystokinin or some other gastrinlike hormone (or all three) may play a previously unrecognized regulatory role with respect to hepatic very low density lipoprotein secretion.

Animals↗

PubMed1992

Lung function and precipitating antibodies in low exposed wood trimmers in Sweden.

Wood trimmers are exposed to molds that periodically grow on timber that may induce alveolitis and obstructive lung disease. We have evaluated respiratory symptoms, bronchial reactivity, and lung function in 28 wood trimmers at a Swedish sawmill and in 19 unexposed office workers. Eleven (sero-positive) of the wood trimmers had precipitating antibodies in peripheral blood against one or several molds. The exposure to dust (median 0.26 mg/m3), viable mold spores (median 2950 cfu/m3), viable bacteria (median 370 cfu/m3), airborne endotoxins (range 0.0015-0.0025 microgram/m3), and terpenes (range 0.4-23 mg/m3) was lower than levels that earlier have been reported to affect lung function. The wood trimmers reported an increased prevalence of cough and breathlessness. They also showed signs of a mild obstructive impairment with a tendency to increase bronchial sensitivity to metacholine and decreased FEV1 after 2 days free from exposure. FEV1 decreased more during the working week in the sero-positive workers than among the sero-negative workers, and for the whole group the decrease in FEV1 and MEF25 was correlated to the degree of mold exposure.

Adult↗

PubMed1992

Restricted V alpha 2.3 gene usage by CD4+ T lymphocytes in bronchoalveolar lavage fluid from sarcoidosis patients correlates with HLA-DR3.

The alpha/beta T cell receptor (TcR) V gene usage of bronchoalveolar lavage (BAL) lymphocytes and peripheral blood lymphocytes (PBL) from 11 sarcoidosis patients and 4 healthy controls was investigated, using eight alpha/beta TcR V gene product-specific monoclonal antibodies (mAb). Twenty-seven percent (3/11) of the sarcoidosis patients had a highly significant increase in V alpha 2.3+CD4+ T lymphocytes in the bronchoalveolar space, while displaying normal frequencies of these T cells in peripheral blood. The reactivities with the remaining seven TcR mAb were normal. In the control group, no compartmentalization of any T cells was seen. Four of the patients expressed the HLA-DR3 (w17), DQw2 haplotype. Interestingly, the three patients with distinct signs of compartmentalized V alpha 2.3+CD4+ T cells all expressed this HLA haplotype. Additionally, a fourth patient with pronounced, although less significant, accumulation of V alpha 2.3+CD4+ T cells in the lung, was also HLA-DR3(w17), DQw2+. Expression of V alpha 2.3+CD4+ T cells in BAL of these patients correlated with clinical disease, as revealed on re-analyzing the four patients after 6 months or longer. Predominant TcR V alpha 2.3 gene usage in compartmentalized CD4+ BAL T lymphocytes, linked to HLA-DR3(w17), DQw2 haplotype, may thus indicate presence of a specific antigen localized to the lungs of sarcoidosis patients.

Adult↗

PubMed1992

Increased expression of adhesion proteins (MAC-1) and altered metabolic response in human leukocytes exposed to surfactant in vitro.

In this study the modulatory effects of a well-defined surfactant preparation on blood leukocytes were investigated. The expression of the cell surface receptor MAC-1 was analyzed by flow cytofluorometry, and the metabolic response was measured by a chemiluminescence technique. An increase (p less than 0.05) in the MAC-1 receptor expression was observed in the granulocytes but not in the monocytes. There was a decrease in the metabolic response of the leukocytes after stimulation with phorbol myristate acetate (PMA) and a delay (p less than 0.01 for both) in the peak activity. Formyl-methionyl-leucyl-phenylalanine (fMLP) caused an increased peak (p less than 0.01). Thus, the surfactant preparation had a modulatory effect on blood leukocytes with regard to the expression of the cell surface receptor MAC-1 and the metabolic response.

Adolescent↗

PubMed1992

Signs of alveolar inflammation in non-smoking Swedish wood trimmers.

Wood trimmers are periodically exposed to mould and may develop extrinsic allergic alveolitis (EAA). To investigate if there were any signs of EAA in wood trimmers with low exposure, 19 non-smoking wood trimmers underwent bronchoalveolar lavage (BAL), spirometry, and measurement of diffusion capacity (TLCO). The group was subdivided into those with (n = 9) and without serological antibodies against mould. In 14 workers the TLCO was measured both at the beginning and at the end of a week at work. Twenty five healthy non-smokers served as BAL controls and 19 healthy non-smokers as lung function controls. The median exposure of total dust was well below the Swedish threshold value, and the exposure of mould and bacteria was also low. The cell concentrations and the proportions of the various alveolar cells did not differ between the groups. The concentrations of the soluble components albumin, fibronectin, and hyaluronan were, however, significantly increased (p less than 0.001 for all) in the workers. No difference was found in lung function between the workers and the controls, and the TLCO was not impaired during a week at work. The groups of seropositive and seronegative workers did not differ in any of these parameters. The results are interpreted as a low intensity alveolar inflammation. The presence of precipitating antibodies against mould did not predict any greater risk of developing a more intense inflammation. Analysis of soluble non-cellular BAL components seems to reflect a discrete ongoing alveolar inflammation better than cell counts only.

Adult↗

PubMed1992

Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.

Acute Disease↗

PubMed1992

Alterations in bronchoalveolar lavage fluid but not in lung function and bronchial responsiveness in swine confinement workers.

Testing of lung function and bronchial reactivity, bronchoalveolar lavage (BAL), and a skin prick test with a standard panel and six "swine" extracts obtained from swine and swine environment were performed in 20 randomly selected nonsmoking swine confinement workers. In addition, blood samples for detection of antibodies by the diffusion in gel-enzyme-linked immunosorbent assay (DIG-ELISA) technique and precipitating antibodies were drawn. Air samples for measurement of dust and endotoxin levels were collected. All the farmers regarded themselves as healthy. The results were compared with reference groups consisting of urban nonsmoking subjects who had not been exposed to pig farming environment. The pig farmers had normal lung function and the bronchial reactivity was not different from the reference group. In the BAL fluid of the farmers, the concentration of total cells and granulocytes was increased while the concentrations of lymphocytes and macrophages were normal. The BAL fluid concentrations of albumin, fibronectin, and hyaluronan were elevated in the farmers. Skin prick tests with swine extracts were negative in all farmers. Antibodies (assessed by DIG-ELISA) against swine dander, swine dust, and pig feed were increased and precipitating antibodies against swine dander were found in 14, against pig food in five, and against swine confinement dust in three of the 20 pig farmers. The concentration of airborne total dust was 7.4 mg/cu mm and the endotoxin concentration was 37 (22 to 60) ng/cu mm during tending the pigs and increased, during feeding, to 13.8 mg/cu mm and 315 (194 to 716) ng/cu mm, respectively. There was no correlation between exposure and lung function or lavage findings. In conclusion, randomly selected pig farmers had signs of airway inflammatory reaction and activation of the immune system without alteration in lung function and bronchial reactivity.

Adult↗

PubMed1992

Smoking cessation rapidly reduces cell recovery in bronchoalveolar lavage fluid, while alveolar macrophage fluorescence remains high.

Bronchoalveolar lavage (BAL) was performed in smokers (22.6 +/- 7.8 pack-years) before (n = 18) and 1 (n = 14), 3 (n = 13), 6 (n = 11), 9 (n = 9), and 15 (n = 8) months after smoking cessation. The recovery of the BAL fluid increased after smoking cessation (p less than 0.05). The total number of cells and the cell concentration were significantly lower already at one month (p less than 0.05 and p less than 0.01, respectively), and this decline was more pronounced at the following lavages. By using flow cytofluorometry, alveolar macrophage (AM) fluorescence was quantified, since it is known that AMs lavaged from smokers have an increased fluorescence, due to interaction with fluorescent substances in the inhaled smoke. Not until six months after smoking cessation was a significant (p less than 0.05) decrease in AMs fluorescence noted. At 15 months, the fluorescence was still increased, with great individual variations, compared with AMs from nonsmokers. The decline in fluorescence of AMs after smoking cessation was negatively correlated to the previous cigarette consumption. The absence of new, low fluorescent cells in the BAL fluid, despite a slow, but significant decrease in the fluorescence intensity of the whole cell population, suggests that the fluorescent material is redistributed from older AMs to newly recruited cells. These substances can thus remain in the alveolar space for a longer time than the estimated life span of the AMs.

Adult↗

PubMed1992

Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions.

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction.

Aged↗