1.
Greiff, Lennart, et al.
(author)
Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
1997
In: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
Journal article (peer-reviewed) abstract
Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
2.
Korsgren, Magnus, et al.
(author)
Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice
1997
In: Journal of Experimental Medicine. - 1540-9538. ; 185:5, s. 885-892
Journal article (peer-reviewed) abstract
Immunoglobulins (Ig), particularly IgE, are believed to be crucially involved in the pathogenesis of asthma and, equally, in allergic models of the disease. To validate this paradigm we examined homozygous mutant C57BL/6 mice, which are B cell deficient, lacking all Ig. Mice were immunized intraperitoneally with 10 micrograms ovalbumin (OVA) plus alum, followed by daily (day 14-20) 30 min exposures to OVA aerosol (OVA/OVA group). Three control groups were run: OVA intraperitoneally plus saline (SAL) aerosol (OVA/SAL group); saline intraperitoneally plus saline aerosol; saline intraperitoneally plus OVA aerosol (n = 6-7). Lung and large airway tissues obtained 24 h after the last OVA or SAL exposure were examined by light microscopy and transmission electron microscopy (TEM). The Ig-deficient mice receiving OVA/ OVA treatment had swollen and discolored lungs and exhibited marked eosinophilia both in large airway subepithelial tissue (49.2 +/- 12.0 cells/mm basement membrane [BM] versus OVA/ SAL control 1.2 +/- 0.3 cells/mm BM; P < 0.001), and perivascularly and peribronchially in the lung (49.3 +/- 9.0 cells/unit area versus OVA/SAL control 2.6 +/- 0.6 cells/unit area; P < 0.001). The eosinophilia extended to the regional lymph nodes. TEM confirmed the subepithelial and perivascular localization of eosinophils. Mucus cells in large airway epithelium increased from 1.5 +/- 0.8 (OVA/SAL mice) to 39.5 +/- 5.7 cells/mm BM in OVA/OVA treated mice (P < 0.001). OVA/SAL mice never differed from the other control groups. Corresponding experiments in wild-type mice (n = 6-7 in each group) showed qualitatively similar but less pronounced eosinophil and mucus cell changes. Macrophages and CD4+ T cells increased in lungs of all OVA/OVA-treated mice. Mast cell number did not differ but degranulation was detected only in OVA/OVA-treated wild-type mice. Immunization to OVA followed by OVA challenges thus cause eosinophil-rich inflammation in airways and lungs of mice without involvement of B cells and Ig.
3.
Persson, Carl, et al.
(author)
The mouse trap
1997
In: Trends in Pharmacological Sciences. - 0165-6147. ; 18:12, s. 465-467
Journal article (peer-reviewed) abstract
Mouse models of asthma are now being used extensively in drug research. However, the successful unravelling of combinatorial interplays of cells and molecules in the murine airways may not be matched by equally successful demonstrations of an asthma-like pathophysiology. Here, Carl Persson, Jonas Erjefalt, Magnus Korsgren and Frank Sundler discuss the fact that major features of asthma may still need to be demonstrated in the airways of allergic mice.
4.
Gustafsson, Lars, et al.
(author)
Infectious disease, reproductive effort and the cost of reproduction in birds
1994
In: Philosophical transactions of the Royal Society of London: Series B. ; :346, s. 1655-1658
Journal article (pop. science, debate, etc.) abstract
Reproductive effort can have profound effects on subsequent performance. Field experiments on the collared flycatcher (Ficedula albicollis) have demonstrated a number of trade-offs between life-history traits at different ages. The mechanism by which reproductive effort is mediated into future reproductive performance remains obscure. Anti-parasite adaptations such as cell-mediated immunity may probably also be costly. Hence the possibility exists of a trade-off between reproductive effort and the ability to resist parasitic infection. Serological tests on unmanipulated collared flycatchers show that pre-breeding nutritional status correlates positively with reproductive success and negatively with susceptibility to parasitism (viruses, bacteria and protozoan parasites). Both immune response and several indicators of infectious disease correlate negatively with reproductive success. Similar relations are found between secondary sexual characters and infection parameters. For brood-size-manipulated birds there was a significant interaction between experimentally increased reproductive effort and parasitic infection rate with regard to both current and future fecundity. It seems possible that the interaction between parasitic infection, nutrition and reproductive effort can be an important mechanism in the ultimate shaping of life-history variation in avian populations.
5.
Greiff, Lennart, et al.
(author)
Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
1999
In: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
Journal article (peer-reviewed) abstract
Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
6.
Sadziene, Ariadna, et al.
(author)
A bactericidal antibody to Borrelia burgdorferi is directed against a variable region of the OspB protein
1994
In: Infection and Immunity. - : American Society for Microbiology (ASM). - 0019-9567 .- 1098-5522. ; 62:5, s. 2037-2045
Journal article (peer-reviewed) abstract
Borrelia burgdorferi, an agent of Lyme disease, is killed by some monoclonal antibodies in the absence of complement or phagocytes. In the present study, the bactericidal action of monoclonal antibodies against B. burgdorferi and B. hermsii, a cause of relapsing fever, was further characterized. H6831, an antibody recognizing the OspB proteins of some B. burgdorferi strains, and H4825, an antibody specific for one serotype of B. hermsii, were purified, and Fab fragments of the antibodies were prepared. In time-kill studies, more than 99.9% of strain B31 B. burgdorferi cells were killed after 30 min of exposure to H6831 Fab fragments. The MBC of the Fab fragments was 10 micrograms/ml. Electron microscopy revealed that the bactericidal Fab fragments produced numerous blebs and cell lysis of the borrelias for which they were specific. To identify the epitope for H6831, the OspB sequences of H6831-susceptible and -resistant strains and mutants were determined. The deduced OspB proteins of all H6831-resistant strains and mutants differed from the strain B31 OspB at residue 253. Murine antisera raised against a 21-mer synthetic peptide representing the region around residue 253 were specific for strain B31 by Western blot (immunoblot) and growth inhibition assays. Furthermore, the antipeptide serum inhibited the binding of H6831 to whole borrelias. These findings indicated that the linear component of the bactericidal antibody's epitope was located at or near residue 253.
7.
Aniansson, Gustaf
(author)
Breast-feeding, nasopharyngeal colonization and otitis media.
1999
Doctoral thesis (other academic/artistic) abstract
This thesis analyzed the relationship between breastfeeding, nasopharyngeal colonization and acute otitis media (AOM) in children. Nasopharyngeal cultures were collected from 400 children and milk samples from their mothers in connection with the scheduled visits to well baby clinics at 1-3, 4-7 and 8-12 months of age, and episodes of AOM and URI were documented. The nasopharyngeal flora was acquired more slowly by Swedish infants than in developing countries. The carriage increased with the number of siblings and day care center. (Aniansson et al. J Infect Dis. 1992;165:38-42). Breast-feeding was associated with a reduced frequency of AOM and URI, but the frequencies were higher in children with day-care contact and siblings. The nasopharyngeal bacterial carriage was higher in children with AOM. (Aniansson et al .Pediatr Infect Dis. J 1994;13:83-188). The pneumococcal anti-capsular antibody activity, in milk samples collected from the nursing mothers, was low or absent in >90% of the milk samples. In contrast anti-phosphorylcholine and anti-cell wall polysaccharide antibody activity was common. The frequency of AOM did not vary with the milk antibody activity (Andersson v Rosen et al. Pediatr Infect Dis J. 1996;15:498-507). The pneumococcal isolates were tested for adherence to human respiratory tract epithelial cells. Adhesive capacity was found in virtually all isolates. Anti-adhesive activity was found in 98.8% of the individual milk samples and it increased with age (Aniansson et al. Submitted). Children with a cleft palate were investigated between 6 and 10 years of age. Despite surgical repair and early treatment with a tympanic membrane tube, AOM and secretory otitis media were common, presumably due to Eustachian tube dysfunction and premature cessation of breast-feeding (Aniansson et al. Submitted).
8.
Håkansson, Anders
(author)
Apoptosis induced by a human milk protein complex. Cellular and structural studies in tumour cells and bacteria.
1999
Doctoral thesis (other academic/artistic) abstract
Human milk contains a vast array of bioactive molecules, with nutritional and protective functions. This thesis describes the effects of a human milk protein complex, MAL, on tumour cells and bacteria. During our studies on the anti-adhesive properties of human milk we observed that a milk fraction killed tumour cells. The morphology of the cells indicated apoptotic cell death and this was verified by DNA fragmentation analysis (Proc Natl Acad Sci U.S.A 1995; 92: 8064-8068). The effect of MAL was selective for tumour cells and immature embryonic cells while mature differentiated cells were resistant. MAL bound to the surface of both sensitive and resistant cells but was internalised only in sensitive cells. MAL was shown to co-localise with mitochondria and this interaction caused a disruption of the mitochondrial membrane potential, which caused release of cytochrome c and caspase activation (Exp Cell Res 1999; 249: 260-268). The caspase activation was functional as shown by the cleavage of intracellular substrates. In parallel MAL was also transported via active nuclear transport to the nuclei of sensitive cells. MAL exerted a direct effect on isolated nuclei causing the induction of apoptotic DNA fragmentation without involvement of mitochondrial activation pathways (Exp Cell Res 1999; 2246: 451-460). MAL was purified from the casein fraction of human milk and was shown by N-terminal amino acid sequencing to contain alpha-lactalbumin. Native alpha-lactalbumin had no bactericidal or tumouricidal activity, suggesting that the alpha-lactalbumin of the active fraction had different structural properties. By spectroscopic techniques MAL was shown to have a more flexible tertiary structure with exposure of hydrophobic surfaces like the molten globule form of alpha-lactalbumin (J Biol Chem 1999; 274: 6388-6396). Native alpha-lactalbumin was inactive, but could be converted to the active form by a folding change combined with a fatty acid to stabilise this fold. These studies verified that alpha-lactalbumin was the active component and that the conformational change was required for the apoptosis-inducing activity. MAL was also shown to be bactericidal against S. pneumoniae, but had little effect against gram-negative and other gram-positive bacteria. In S. pneumoniae MAL was shown to induce identical DNA fragmentation as seen in tumour cells, suggesting apoptosis-like features of bacterial death. The bacterial death did not involve cytochrome c and caspase-activation but the bacteria had sequence homologies in three open reading frames of the pneumococcal genome with a caspase-independent effector molecule in eukaryotic cells, apoptosis inducing factor (AIF). These sequences are currently investigated.
9.
10.
Lodinová-Zádníková, R, et al.
(author)
The antibody response in breast-fed and non-breast-fed infants after artificial colonization of the intestine with Escherichia coli O83.
1991
In: Pediatric research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 29:4 Pt 1, s. 396-9
Journal article (peer-reviewed) abstract
The local and systemic antibody response after oral administration of a nonenteropathogenic type 1 fimbriated Escherichia coli O83 strain was followed in nine breast-fed and eight formula-fed infants during their first 15 wk of life. Five breast-fed and six formula-fed infants were followed as controls. E. coli O83 was detected in the stools of colonized infants from d 2 after colonization and persisted in the intestine for up to 26 wk. The percentage of children successfully colonized with E. coli O83 was higher among breast-fed than among formula-fed colonized infants. Also, the O83 bacteria isolated from the breast-fed children had a higher capacity to attach to colonic epithelial cells of the HT-29 cell line than those isolated from bottle-fed infants. E. coli O83 IgA and IgM antibodies estimated by ELISA were significantly elevated in the saliva of colonized as compared with control infants 2-7 wk after colonization. IgA antibodies against O83 were also higher in the stool of colonized formula-fed infants than in formula-fed controls. The results suggest that the mucosal immune system of the newborn infant can be triggered early to produce specific antibodies against bacteria colonizing the intestine.
