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Am J Physiol Endocrinol Metab. 2002 Nov;283(5):E899-908.
Effect of endotoxin on expression of TNF receptors and transport of TNF-alpha at the blood-brain barrier of the rat.

Osburg B, Peiser C, Domling D, Schomburg L, Ko YT, Voigt K, Bickel U.

Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.

The transport mechanism mediating brain uptake of tumor necrosis factor (TNF)-alpha has been studied. When (125)I-labeled rat TNF-alpha was used in internal carotid artery perfusions in rats, the cytokine showed transcytosis through the blood-brain barrier in intact form (permeability-surface area product 0.34 +/- 0.13 microl. min(-1). g(-1)). Uptake was inhibited by low nanomolar concentrations of unlabeled rat TNF-alpha. Human TNF-alpha, which does not interact with the p80 TNF receptor in rodents, showed no brain uptake. mRNA expression of both p60 and p80 receptors could be demonstrated in native brain microvessel preparations. These transcripts increased to 149% (p60) and 127% (p80) of control 4 h after a systemic immune stimulation (2 mg/kg bacterial endotoxin ip). Lipopolysaccharide treatment did not alter the rate of brain uptake of TNF-alpha measured between 4 and 24 h later. In conclusion, a receptor-mediated mechanism is responsible for the transcytosis of TNF-alpha. Saturable transport, requiring the p80 receptor, occurs at concentrations encountered under pathophysiological conditions and therefore constitutes a relevant mechanism of communication between the immune system and the brain.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12376316&dopt=Abstract

Cell Biol Int. 2002;26(9):817-28.
Specific monoclonal antibodies against the surface of rat islet beta cells.

Konidaris C, Simonson W, Michelsen B, Papadopoulos GK.

Laboratory of Biological Chemistry, University of Ioannina Medical School, GR45100, Ioannina, Greece.

Type 1 diabetes arises from the autoimmune destruction of islet beta cells, with the participation of both arms of the immune system. To better characterize the beta cell membrane, we have raised monoclonal antibodies to the surface of the INS-1 insulinoma cell line. Twenty-two such antibodies were produced, 21 of the IgG class, all reactive to different cell membrane proteins from INS-1 and neonatal islet cells, yielding identical electrophoresis patterns, with molecular weights mainly between 45 and 60 kD. We have focused on three such antibodies that recognize different protein targets, and are specific for islet beta cells. The target protein of antibody AA4, also found on monkey islets, is expressed at significantly higher levels on beta cells (55.8 vs 30.6% of cells, plus 3-4 fold increase in average fluorescence intensity per cell) when neonatal rat islet cells are incubated with high (16 mM vs 3mM) glucose concentrations. Further identification of the target antigens is in progress and is expected to shed more light on the properties of beta cell membrane proteins, and their probable participation in various disease processes.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12377213&dopt=Abstract

Pediatr Allergy Immunol. 2002 Dec;13(6):402-11.
An anthroposophic lifestyle and intestinal microflora in infancy.

Alm JS, Swartz J, Bjorksten B, Engstrand L, Engstrom J, Kuhn I, Lilja G, Mollby R, Norin E, Pershagen G, Reinders C, Wreiber K, Scheynius A.

Sachs' Children's Clinic, Soder Hospital, Stockholm, Sweden. Johan.Alos.ki.se

The intestinal flora is considered to have an impact on the development of the immune system. In the anthroposophic lifestyle, a diet comprising vegetables spontaneously fermented by lactobacilli, and a restrictive use of antibiotics, anti-pyretics and vaccinations, is typical. The aim of this study was to assess the gut flora in infants in relation to certain lifestyle characteristics associated with anthroposophy. Sixty-nine children < 2 years of age with an anthroposophic lifestyle, and 59 infants of a similar age with a traditional lifestyle, were clinically examined and questionnaire replies assessed. Fecal samples were analyzed by bacterial enumeration, bacterial typing through biochemical fingerprinting and by measuring microflora-associated characteristics (MACs). The numbers of colony-forming units (CFU)/g of feces were significantly higher for enterococci and lactic acid bacteria in children who had never been exposed to antibiotics (5.5 x 107 vs. 2.1 x 107; p < 0.001 and 10 x 107 vs. 4.1 x 107; p < 0.01, respectively). Furthermore, the number of enterococci was significantly higher in breastfed and vegetarian infants (p < 0.01). The diversity (Simpson's diversity index) of lactobacilli, as determined by biochemical fingerprinting, was higher in infants born at home than in those born in hospital (p < 0.01). Several MACs were related to specific lifestyle features, and infants with an anthroposophic lifestyle had a higher proportion of acetic acid and a lower proportion of propionic acid in their stool as compared to the control children. In conclusion, lifestyle factors related to the anthroposophic way of life influenced the composition of the gut flora in the infants. These differences may contribute to the lower prevalence of atopic disease previously observed in children in anthroposophic families.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12485315&dopt=Abstract

Dev Comp Immunol. 2002 Nov;26(9):849-60.
Maternal prolactin composition can permanently affect epidermal gammadeltaT cell function in the offspring.

Yang L, Lii S, Kuo B, Buckley A, Buckley D, Chen C, Xu X, Coss D, Walker AM.

Division of Biomedical Sciences, University of California, Riverside, CA 92521-0121, USA.

There have been few studies aimed at determining the effects of maternal peptide hormones on the developing fetus and even fewer aimed at determining the long-term consequences of abnormalities in maternal hormone exposure. In this study, we have examined the effect of maternal prolactin (PRL) on the production, seeding and long-term function of a T lymphocyte subset for which the precursors are only present during fetal life. Using this system, we can determine long-term consequences of maternal hormone exposure without concern for the subsequent influence of the offspring's endocrine milieu. Recombinant versions of the two major forms of the pituitary hormone, PRL, were administered to rats throughout pregnancy. Administration of a molecular mimic of phosphorylated PRL (PP-PRL) resulted in a marked increase in the level of apoptosis in the thymus of newborn pups, an effect that was not duplicated by administration of unmodified PRL. The increased thymic apoptosis in the animals exposed to PP-PRL resulted in decreased epidermal seeding of gammadeltaT cells and a markedly decreased gammadeltaT cell-modulated epidermal response in the offspring. This decreased gammadeltaT cell modulated response persisted to adulthood. We conclude that maternal PRL composition during pregnancy can have a permanent effect on at least one component of the developing immune system.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12377224&dopt=Abstract

J Leukoc Biol. 2002 Oct;72(4):810-8.
The chemoattractant Trp-Lys-Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1.

Svensson L, Dahlgren C, Wenneras C.

Department of Clinical Bacteriology, Sahlgrenska University Hospital, Goteborg, Sweden.

Whereas prokaryotes use L- and D-isomers of amino acids in their protein synthesis, eukaryotic proteins as a rule incorporate only L-isomers. Hence, D-isomers may constitute danger signals to the innate immune system. A D-methionine-containing peptide, Trp-Lys-Tyr-Met-Val-D-Met-NH(2) (WKYMVm), has been shown to be a stronger activator of neutrophils than f-Met-Leu-Phe. The aim of this study was to compare the responsiveness of eosinophils to WKYMVm with that of neutrophils. The peptide was found to induce chemotaxis and respiratory burst in eosinophils. However, it did not mobilize granule constituents, as evidenced by a lack of eosinophil cationic protein, eosinophil peroxidase, and interleukin-5 in the supernatants of stimulated eosinophils. In contrast, WKYMVm caused the release of complement receptor 3 from secretory vesicles in neutrophils. Different members of the formyl peptide receptor family were preferentially engaged by the peptide in the two classes of granulocytes: the formyl peptide receptor itself in eosinophils and formyl peptide receptor-like 1 in neutrophils.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12377951&dopt=Abstract

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