Biomedical subjects

J Lundahl

Publications and source records attributed to J Lundahl.

At least 73 records · Page 4Linked to original sources

PubMed1998

No evidence for increased frequency of autoantibodies during interferon-beta1b treatment of multiple sclerosis.

Interferon-beta1b (IFN-beta1b) is a widespread therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. Since IFN-beta1b has potent immunomodulatory properties, a potential side-effect of IFN-beta1b treatment could be the development of autoimmune responses. The frequencies of antinuclear and smooth muscle antibodies, antibodies against microsomal antigen of thyroid epithelial cells as well as a group of heterophilic antibodies were determined in 26 MS patients treated with IFN-beta1b for 3-20 months. No elevation of antibody titres was found for any of the antibodies studied when compared with paired samples obtained from most of the patients before the initiation of treatment. Although examined on a rather small group of patients, the results show no evidence of increased frequency of autoantibodies during interferon-beta1b treatment of multiple sclerosis.

Adjuvants, Immunologic↗

PubMed1998

Differences between rat alveolar and interstitial macrophages 5 wk after quartz exposure.

Macrophages play an essential role in pulmonary host defense. We investigated differences between rat alveolar (AM) and interstitial (IM) macrophages after exposure in vivo to quartz, an inducer of intensive alveolitis. Rats were exposed to 0.5 ml of saline without (n = 8) or with (n = 8) 10 mg of quartz by intratracheal instillation. In a third group (n = 8), 10 mg of surfactant were added to the quartz mixture. Five weeks later, AM were recovered by bronchoalveolar lavage and IM by mechanical fragmentation of the lung, followed by enzymatic treatment. Contamination of AM to the IM fraction was calculated to be 12-15%. After quartz exposure, the expression of major histocompatibility complex class Ia was increased in both AM and IM fractions. The receptor corresponding to human complement receptor 3 increased in AM after quartz exposure, and AM from quartz-exposed animals had a lower metabolic activation. Our findings indicate that IM are immunocompetent cells and that differences between AM and IM fractions occur upon quartz-induced inflammation. This response is not affected by addition of surfactant.

Animals↗

PubMed1998

Complement activation during blood sampling procedures alters the expression of CD11b/CD18 on human neutrophils.

BACKGROUND AND OBJECTIVES: Differences in blood sampling and separation techniques can affect the quantitative levels of activation markers on different leukocyte subsets. We examined the effect of two sampling procedures of EDTA blood on the quantitative levels of two markers, the CD11b/CD18 antigen and the EG2 epitope on intracellular eosinophilic cationic protein (ECP), in neutrophils and eosinophils, respectively. MATERIALS AND METHODS: Sample I was collected directly after completion of blood donation by an open technique and constant flow from the transfer tube directly into EDTA tubes. After sampling, the transfer tube was manually closed with a clamp. Sample II was collected 45 s later by the same technique by opening the clamp. RESULTS: We found a significantly (p < 0.01) higher expression of CD11b/CD18 on neutrophils collected by sampling procedure II than on those collected by sampling procedure I. In contrast, we did not find any difference in the intracellular ECP expression between sampling procedures I and II. To further explore the mechanisms for the observed upregulation of CD11b/CD18, fragments of a transfer tube were incubated with normal human serum (NHS) and heat-inactivated NHS (NHS56), respectively, for 60 min at +37 degrees C. Leukocytes from healthy blood donors were then incubated for 15 min at +37 degrees C with these serum preparations. The CD11b/CD18 expression was significantly higher (p < 0.01) on neutrophils incubated with transfer-tube-activated NHS compared with NHS alone. However, when leukocytes were incubated with transfer tube activated NHS56, no difference was observed compared with incubation with NHS alone. In addition, by using confocal laser scanning microscopy, we could identify complement (C3c) deposits on the inner surface of the transfer tube fragments incubated in NHS, but not in NHS56, CONCLUSIONS: The quantitative level of the activation marker CD11b/CD18 on neutrophils, but not the EG2 epitope on intracellular ECP in eosinophils is significantly increased by a slight modification of the blood sampling procedure. It is suggested that the observed upregulation of CD11b/CD18 is caused by complement activation within the transfer tube. The results emphasize the importance of in-house data on the effect of variations in sampling procedures, particularly when data from healthy blood donors are included in clinical studies.

Blood Proteins↗

PubMed1998

Kinetics of bradykinin levels during and after leucocyte filtration of platelet concentrates.

OBJECTIVE: To measure bradykinin levels in platelet concentrates during and after leucocyte filtration. METHODS: Platelet concentrates were leukocyte depleted using three different leucocyte-depletion filters selected to represent filters with negative, positive or neutral charge, respectively. Bradykinin levels were analysed before, during and up to 90 min post-filtration. RESULTS: Significant levels of bradykinin were generated when negatively charged leucocyte depletion filters were used. However, we found a high variation between platelet concentrates prepared from different donors as well as within the same concentrate when this was divided into three aliquots. Generated bradykinin was rapidly degraded in the collection bag and no bradykinin was detectable 60 min post-filtration. CONCLUSION: Bradykinin generation is more pronounced when negatively charged leucocyte removal filters are used. Due to a rapid degradation of bradykinin in the storage bag, pre-storage filtration should minimise the risk of bradykinin related adverse reactions during transfusion with some filters.

Adolescent↗

PubMed1997

Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men.

OBJECTIVE: To examine the effect of grapefruit juice on the metabolism of felodipine following intravenous and oral administration. METHODS: The study had a randomised, four-way, crossover design in 12 healthy males. Single doses of felodipine were given as an intravenous infusion for 1 h (1.5 mg) or as an oral extended release (ER) tablet (10 mg). Grapefruit juice (150 ml) or water was ingested 15 min prior to drug intake. RESULTS: Intake of grapefruit juice did not significantly alter the intravenous pharmacokinetics of felodipine compared to control treatment, whereas after oral drug administration it did lead to an increase in the mean AUC and Cmax by 72% and 173%, respectively, and the mean absolute bioavailability was increased by 112%. The fraction of the oral felodipine dose reaching the portal system was increased from 45% to 80% when intake of drug was preceded by grapefruit juice ingestion. The pharmacokinetics of the primary metabolite, dehydrofelodipine, was affected by the intake of juice, resulting in a 46% increase in Cmax. Juice intake immediately before oral felodipine resulted in more pronounced haemodynamic effects of the drug as measured by diastolic blood pressure and heart rate. However, the haemodynamic effects of the intravenous administration were not altered by juice intake. Vascular-related adverse events were reported more frequently when oral drug administration was preceded by juice intake compared with control treatment. Taking grapefruit juice immediately prior to intravenous felodipine administration did not cause any alteration in the adverse event pattern. CONCLUSION: The main acute effect of the grapefruit juice on the plasma concentrations of felodipine is mediated by inhibition of gut wall metabolism.

Administration, Oral↗

PubMed1997

Dialysis-induced serum factors inhibit adherence of monocytes and granulocytes to adult human endothelial cells.

In patients on hemodialysis, the sequences of events required for adhesion molecule-mediated adherence of monocytes and granulocytes to endothelial cells are pathophysiologically disrupted because activation of the cells with subsequent alterations in adhesion molecule phenotypes takes place in the extracorporeal circuit far away from the respective endothelial cell ligand. As a consequence, the host defense to infections may be affected. We analyzed the expression of CD62L and CD11b/CD18 on monocytes and granulocytes and the adherence of these cells, collected before, during, and after cuprophan hemodialysis, to resting and interleukin-1 beta (IL-1 beta)-stimulated adult human saphenous vein endothelial cells (HSVECs). Monocytes collected before dialysis adhered more avidly to HSVECs than did granulocytes. Adherence of both cell types increased to IL-1 beta-stimulated HSVECs (P < 0.05). Granulocytes obtained at 180 minutes adhered less to resting HSVECs than granulocytes harvested before hemodialysis (P < 0.05), despite an increase in CD11b/CD18 expression. To study if serum factors inhibiting adherence accumulate during hemodialysis, we incubated leukocytes harvested before hemodialysis in the same patients' serum collected before, during, and after dialysis. Serum collected at 180 minutes of cuprophan hemodialysis exerted inhibitory effects on both monocyte and granulocyte adhesion to HSVECs (P < 0.05). By contrast, serum collected during polysulfone hemodialysis of the same patients did not have any significant impact on the adherence of inflammatory cells to HSVECs. These findings contribute to an increased understanding of the factors involved in the impaired immune response observed in dialysis patients.

Adult↗

PubMed1997

Surfactant prevents quartz induced down-regulation of complement receptor 1 in human granulocytes.

Quartz is known to induce an inflammatory response in the alveolar space by recruitment of different effector cells. We investigated the interaction between granulocytes and quartz with respect to expression of complement receptor type 1 (CR1) and CR3, with and without the presence of surfactant. Granulocytes from hemolyzed blood were stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), which mobilize the intracellular pool of CR1 to the surface, and the mean fluorescence intensity (MFI) measured by cytofluorometry was 47.4 (46-63.6) (median; interquartile range). Quartz exposure reduced the CR1 expression to 23.2 (22.8-30.6) MFI units (P < 0.01), a porcine surfactant preparation added during quartz exposure abolished the down-regulation completely, 47.7 (43.2-62.3) MFI units (P < 0.001). Similar results were obtained after preincubation of the cells with surfactant followed by quartz exposure. No significant influence on CR1 expression was found by a synthetic lipid mixture, nor was the CR3 expression affected. In conclusion, this study demonstrates that the presence of surfactant inhibits quartz induced down-regulation of CR1 on activated granulocytes.

Adolescent↗

PubMed1997

Impaired leucocyte rolling, adhesion and transendothelial migration following cuprophane haemodialysis.

In this study, we investigated how different steps in the extravasation process of leucocytes, i.e. rolling, adhesion and transendothelial migration, are affected by haemodialysis with cuprophane membranes. Human leucocytes obtained from whole blood prior to clinical haemodialysis and from the afferent blood line (post-dialyser) 15 min after the initiation of dialysis were injected into the mesenteric microcirculation of urethane anaesthetized rabbits and analysed for their ability to roll in the microvessels by use of intravital fluorescence microscopy. Moreover, neutrophils from the two leucocyte populations were compared with respect to chemoattractant-induced adhesion and transmigration across confluent monolayers of bovine aortic endothelial cells. Our results show that, as compared with pre-dialysis leucocytes, 15 min of cuprophane haemodialysis impaired leucocyte rolling by 78 +/- 7%, reduced N-formyl-methionyl-leucyl-phenylalanin (fMLP)-induced adhesion by 34 +/- 9%, and abolished transendothelial migration. These findings demonstrate that intradialytical activation of leucocytes during cuprophane haemodialysis severely affects leucocyte functions that are critical in the extravasation process of these cells at inflammatory tissue sites, and thus may help explain the increased susceptibility to infections observed in patients on chronic haemodialysis.

Animals↗

PubMed1997

Phenotypic alterations in circulating monocytes induced by open heart surgery using heparinized and nonheparinized cardiopulmonary bypass systems.

In this study of 31 patients with coronary bypass surgery, we used flow cytometry to compare heparin-coated and noncoated cardiopulmonary bypass systems on leukocyte activation. We found significant differences between the groups during bypass, with activation of the complement system, measured as elevated levels of C3a desArg, upregulation of granulocyte beta2 integrin (CD11b), and a loss of circulating monocytes when noncoated systems were used. In both groups an early increase in the monocyte cell surface CD62L expression was obvious while the percentage of human leukocyte antigen (HLA)-DR positive monocytes did not alter. The morning after the operation, leukocytosis was present, together with a highly significant reduction in the monocyte expression of CD11b and HLA-DR, indicating the recruitment to the peripheral blood of cells with altered phenotypes. This alteration in phenotype on potent inflammatory cells may be one part of the impaired function of the immunological system reported after major surgery.

Adult↗

PubMed1997

Different expression and mobilisation of the complement regulatory proteins CD35, CD55 and CD59 in neonatal and adult neutrophils.

We investigated the expression and the N-formyl-methionyl-phenylalanine (fMLP)- and interleukin-8 (IL-8)-induced mobilisation of the complement regulatory proteins CR1 (CD35), decay-accelerating factor (CD55) and CD59 on neutrophils in neonates and adults. The expression of CD35 on resting neonatal neutrophils was significantly higher than in adults. Both fMLP and IL-8 increased CD35 expression more markedly in adults. CD55 on resting neutrophils in neonates was significantly higher than in adults, but did not further increase upon fMLP stimulation as opposed to adults. The increase in CD59 expression was more pronounced in adult neutrophils and was significantly higher than in neonates after fMLP activation. The addition of the protease inhibitor phenylmethanesulphonyl fluoride during fMLP activation improved the upregulation of CD35 significantly more in neonates, but not CD55 or CD59. This effect could be replaced by human normal sera. These data demonstrate that differences exist between neonatal and adult neutrophils with respect to the expression and mobilisation of functional receptors related to protection from autologous complement lysis and may indicate differences in the efficiency to circumvent complement-mediated cell damage at the inflammatory site.

Adult↗

PubMed1997

Functional, morphological, and phenotypical differences between rat alveolar and interstitial macrophages.

Alveolar macrophages (AM) and interstitial macrophages (IM) from rat lungs were characterized with respect to morphology, phagocytosis, adhesion properties, and phenotype. AM were recovered by lung lavage and IM by treatment of the lung tissue with DNAse and collagenase. The AM were enzyme treated in the same way as the IM. The IM were smaller than AM and had a higher nuclear to cytoplasm ratio. They had markedly lower phagocytic capacity. The attachment of particles to the cell surface was significantly lower in IM than in AM, but the capacity to ingest the particles was the same. Adherence to vitronectin- as well as fibronectin-coated surfaces was significantly higher in AM. The phagolysosomal pH was similar in IM and AM, around pH 5, indicating that dissolution of inorganic particles can take place effectively also in IM. Five surface receptors were studied, and the expression differed significantly in all five between AM and IM. The expression of OX-1 (CD 45), a common leukocyte antigen, was significantly higher on AM as was the expression of CD 71 (transferrin receptor). The receptor density for OX-42 was higher on a fraction of IM. This might be compatible with a stronger interaction between these cells and, for example, matrix components. IM had more surface antigen expressing MHC class Ia (OX-6) and CD 54. Both receptors are important for the antigen presentation capacity of macrophages. These findings show profound differences in phenotype between AM and IM and indicate that IM is a highly immunocompetent cell and should not be regarded only as a precursor to AM.

Animals↗

PubMed1997

Molecular evidence for pap-G specific adhesion of Escherichia coli to human renal cells.

PURPOSE: To study the interaction between class II G-adhesin of Escherichia coli and human urogenital cells. MATERIAL AND METHODS: The adherence of two wild type P-fimbriated E. coli strains, both carrying a class II G-adhesion, and two constructed mutants (one class II G-adhesion knock-out mutant and one class switch mutant in which the papG gene was exchanged with a prsJ96 allele which is a representative of the class III G-adhesin) to human urogenital cells were examined by light microscopy and flow cytometry. RESULTS: The wild type E. coli strains adhered avidly to proximal tubular cells, but the isogenic mutant strains did only adhere in one of the experiments. A soluble receptor analogue inhibited bacterial attachment. CONCLUSIONS: These experiments strongly suggest that the papG class II tip adhesin of P-fimbriae is essential in the pathogenesis of human kidney infection.

Adhesins, Bacterial↗

PubMed1996

Labelling of leucocytes with technetium-99m exametazime causes in vitro upregulation of granulocyte CD11b without correlation to tissue uptake in vivo.

The aims of this study were to investigate whether labelling with technetium-99m exametazime alters the expression of adhesion molecule CD11b on granulocytes and monocytes, and to study whether the expression of CD11b on unlabelled or labelled cells correlates with uptake of the labelled cells in the inflamed bowel, in the lungs or in the reticuloendothelial system. Leucocytes were obtained from 25 patients with inflammatory bowel disease who underwent leucocyte scan. The cellular expression of CD11b was analysed using flow cytometry. Labelling with 99mTc-exametazime induced an increased surface expression of CD11b on granulocytes (P<0.01), but not on monocytes. The increase in CD11b expression on granulocytes was lower than the spontaneous mobilization that occurred at 37 degrees C and correlated neither with this, nor with N-formyl-methionyl-phenylalanine induced expression of the same receptor. Basal expression of CD11b on unlabelled granulocytes, but not on monocytes, correlated with bowel and lung uptake 45 min after reinjection of labelled cells, but not with uptake on later images. No correlation was found between the CD11b expression on labelled granulocytes or monocytes and scintigraphic uptake. Our findings show that labelling with 99mTc-exametazime increases the expression of adhesion protein CD11b on granulocytes. The increase in surface expression of CD11b does not correlate with the scintigraphic uptake of labelled cells in the bowel, in the lungs or in the reticuloendothelial system.

Adult↗

PubMed1996

Endotoxemia and complement activation after severe burn injuries--effects on leukocytes, soluble selectins, and inflammatory cytokines.

In this study we followed the development of an inflammatory response in a group of patients the first week after a burn injury. We detected elevated plasma endotoxin levels, on at least one occasion, in 6 of 8 patients. No endotoxin was detected in the two patients with the lowest total burned surface area (< or = 30%). We found evidence of complement activation as increased C3a levels, in parallel with a production of inflammatory cytokines (TNF-alpha, IL-6). The TNF-alpha levels increased significantly during the observation period, while the IL-6 levels were elevated already at admission, and remained so. Elevated levels of soluble E-selectin were detected, indicating endothelial cell activation. Despite the inflammatory response and a loss of inflammatory cells during the first days of the monitoring period, we found no evidence of cellular activation measured as increased expression of beta 2 integrin CD11b, nor increased plasma levels of soluble L-selectin.

Adolescent↗

PubMed1996

Adhesion properties of human alveolar macrophages with respect to extracellular matrix components and chemotactic agonists.

Adherence has an essential impact on the differentiation and activation of tissue dwelling monocytes/macrophages. We have considered the effect of selected chemotactic agonists (fMLP, RANTES, IL-8) on the adhesion properties of human alveolar macrophages prepared by bronchoalveolar lavage. The macrophages were co-incubated in buffer alone or buffer supplemented with respective agonist, for different time points, in culture wells precoated with albumin, vitronectin and fibronectin, respectively. The macrophages displayed a gradual increase in adhesion in all three surfaces and discriminated between the different matrix components, but did not respond to the selected agonists with increased adhesion.

Adult↗

PubMed1996

Chronic smoke exposure alters the phenotype pattern and the metabolic response in human alveolar macrophages.

Smoking induces a chronic inflammatory process in the lower respiratory tract, where the alveolar macrophages (AM) are the main phagocytes. In the present study, the expressions of different membrane glycoproteins (CD11abc, CD71, CD54, CD14 and CD16) were determined by flow cytometry in AM from smokers and non-smokers after quenching of the intracellular autofluorescence. The metabolic activity of the AM was quantified as a functional test. The expressions of CD11a, CD54 and CD71 were higher in non-smokers' AM than in smokers'. The expressions of CD11b and CD16 were similar between the groups, while the CD11c was higher in smokers' AM compared with non-smokers'. The expression of CD14 was weak in both groups, therefore there was no clear-cut difference between the background and positively labelled cell populations. The metabolic response after in vitro stimulation with the phorbol ester phorbol myristate acetate (PMA) was higher in non-smokers' than in smokers' AM. Our results indicate that chronic exposure to tobacco smoke influences both the expression of AM membrane antigens and the metabolic activity. AM from non-smokers express a phenotype more related to cell proliferation and an accessory function. In contrast, receptors reflecting adhesion and phagocytosis were unaltered or even increased in smokers' AM. The findings suggest a functional change in the AM population after chronic smoke exposure.

Adolescent↗

PubMed1996

Monocyte and neutrophil adhesion to matrix proteins is selectively enhanced in the presence of inflammatory mediators.

The authors investigated the time course of monocyte and neutrophil adhesion to fibronectin, vitronectin and albumin precoated culture wells, using mixed leucocyte populations from healthy blood donors. Moreover, the influence of chemotactic agonists on the adhesion properties as well as the quantitative expression of CD29, CD11b/CD18 and CD61 was analysed by flow cytometry. Different chemotactic agonists were used representing a classical chemotactic agonist (fMLP), and agonists with a preferential effect on monocytes (RANTES) and neutrophils (IL-8), respectively. The authors found a gradual increase in monocyte and neutrophil adhesion to all three surfaces, reaching a plateau at 15 min of incubation. Adhesion to fibronectin was significantly higher at all time points (5, 15 and 60 min, respectively) compared with vitronectin and albumin in both monocytes and neutrophils. Neutrophil adhesion to vitronectin was significantly lower at 60 min compared with 15 min. Monocyte adhesion to albumin was increased by fMLP and RANTES and to vitronectin also by IL-8. Neutrophil adhesion to albumin and vitronectin was increased by fMLP and IL-8, but not RANTES. The adhesion to fibronectin was not altered by any of the chemotactic agonists used. The quantitative levels of CD11b/CD18, but not CD29 and CD61, was increased by fMLP, but not RANTES nor IL-8. The authors conclude that the adhesion of human monocytes and neutrophils to vitronectin and albumin, but not fibronectin, is selectively enhanced by chemotactic agonists and may contribute to the selective accumulation of different leucocyte subsets at the inflammatory site.

Adolescent↗

PubMed1996

Monocyte and granulocyte CD11b/CD18, CD62L expression and sICAM-1 concentration in the interdialytic period.

We studied cell surface modulation of CD11b/CD18 and CD62L on monocytes and granulocytes, sICAM-1 concentrations and the responsiveness of cells to exogenous fMLP in patients in the intra- (0-4 h Cuprophan dialysis) and interdialytic period (5-28 h) and in healthy subjects (0-24 h). The high CD11b/CD18, low CD62L granulocyte phenotype occurred rapidly during dialysis. By contrast, CD62L increased on the subpopulation of monocytes in circulation initially during dialysis and CD11b/CD18 was mobilized much slower. In the interdialytic period, the CD62L/(CD11b/CD18) ratio was reduced up to 12 h after start of treatment on both monocytes and granulocytes. This ratio was significantly lower than in healthy subjects up to 8 h after start of treatment. The responsiveness of granulocytes to exogenous fMLP, in terms of CD11b/CD18 mobilization, was significantly reduced in patients during and after hemodialysis as compared to that on granulocytes obtained from healthy controls. Monocytes were more refractory to fMLP up to 4 h after dialysis. sICAM-1 was significantly increased in patients before dialysis as compared to controls and remained elevated and fairly stable throughout treatment and in the interdialytic period. The variation in the expression of adhesion molecules on monocytes and on granulocytes in the interdialytic period was not related to the presence of activating serum factors remaining in the circulation after treatment. Our findings emphasize the importance of including the interdialytic period in the evaluation of dialysis membrane biocompatibility, especially when effects on monocytes are of interest.

Adult↗