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S Gordon

Publications and source records attributed to S Gordon.

At least 127 records · Page 7Linked to original sources
PubMed1998

A functional soluble form of the murine mannose receptor is produced by macrophages in vitro and is present in mouse serum.

A soluble form of the mannose receptor (sMR) has been found in conditioned medium of primary macrophages in vitro and in mouse serum. sMR was released as a single species, had a smaller size than the cell-associated form, and accumulated in macrophage-conditioned medium, in a cytokine-regulated manner, to levels comparable with those found for cell-associated mannose receptor. Pulse-chase experiments showed that sMR production in culture occurred by constitutive cleavage of pre-existing full-length protein. A binding assay was developed to determine the sugar specificity of sMR and its ability to interact with pathogens and particulate antigens (i.e. Candida albicans and zymosan). Protease inhibitor studies suggested that sMR was produced by cleavage of an intact mannose receptor by a matrix metalloprotease or ADAM metalloprotease. A role for sMR in the immune response is proposed based on its binding properties, regulation by cytokines, and the previous discovery of putative ligands for the cysteine-rich domain of the mannose receptor in lymph nodes and spleen.

Amino Acid Sequence↗
PubMed1998

Studies of dehydroepiandrosterone (DHEA) with the human estrogen receptor in yeast.

Dehydroepiandrosterone (DHEA) is a C19 adrenal steroid synthesized in the human adrenal cortex and serving as a biosynthetic precursor to testosterone and 17beta-estradiol. Despite the fact that it is one of the most abundant steroid hormones in circulation, the physiological role of DHEA in humans remains unclear. The action of DHEA itself, such as its interactions with receptors and nuclear transcription factors, is not well understood, and a specific DHEA receptor has yet to be identified. Although the activity of DHEA can be due to its metabolism into androgens and estrogens, DHEA has been shown to interact with the androgen receptor and the estrogen receptor (ER) in vitro. We demonstrate in this study that DHEA (3beta-Hydroxy-5alpha-androstan-17-one) inhibits 17beta-estradiol (E2) binding to its receptor in vivo in yeast. DHEA stimulates human ER dimerization in yeast, as determined by ER fusion protein interactions, GAL4 reconstitution and subsequent measurement of increased beta-galactosidase activity. DHEA causes an increase in estrogen response element-dependent beta-galactosidase activity, demonstrating that the ER dimer induced by DHEA is transcriptionally active, but at a concentration of DHEA about 1000 times greater than E2. Inclusion of the nuclear receptor co-activator RIP140 in the yeast enhances ER transactivation by DHEA or E2 in a ligand-dependent manner; moreover, only in the presence of RIP140 is DHEA able to stimulate beta-galactosidase activity to levels similar to those achieved by E2. Ligand-receptor interaction for other C19-steroids was also examined. While 5-androstene-3beta, 17beta-diol (ADIOL) displayed estrogenic activity in this system, 4-androstene-17-dione (androstenedione) and 4-androstene-17beta-ol,3-one (testosterone) did not. We have investigated whether DHEA can interact with the human ER in vivo. Our findings demonstrate a mechanism by which DHEA interacts directly with estrogen signaling systems; however, because DHEA is several orders of magnitude less potent than E2 in this system, we conclude that it essentially is not an estrogen agonist.

Dehydroepiandrosterone↗
PubMed1998

Cloning of a novel C-type lectin expressed by murine macrophages.

We report the cloning of a novel macrophage-restricted C-type lectin by differential display polymerase chain reaction. This molecule, named mouse macrophage C-type lectin, is a 219-amino acid, type II transmembrane protein with a single extracellular C-type lectin domain. Northern blot analysis indicates that it is expressed in cell lines and normal mouse tissues in a macrophage-restricted manner. The cDNA and genomic sequences of mouse macrophage C-type lectin indicate that it is related to the Group II animal C-type lectins. The mcl gene locus has been mapped between the genes for the interleukin-17 receptor and CD4 on mouse chromosome 6, the same chromosome as the mouse natural killer cell gene complex.

Amino Acid Sequence↗
PubMed1998

Expression and function of the type 3 complement receptor in tissues of the developing mouse.

Macrophage (Mphi) expression of the leukocyte integrins has been implicated in their adhesion and migration in the adult. Little is known, however, of the expression or function of these molecules during development. This study defines the spatial and temporal sequences of expression of the type 3 complement receptor (CR3) in the developing mouse; establishes the functional efficacy of this molecule in spreading, adhesion, and phagocytosis; and investigates its role in inflammatory and constitutive migration. Expression of CR3 on monocytes occurred early compared to Mphi-restricted glycoprotein F4/80, but expression on stellate tissue Mphi appeared later than F4/80 and was transient. Expression of CR3 on resident tissue Mphi is more widespread during development, being retained on only very specific Mphi populations in the adult. Neutrophil polymorphs expressed CR3 from day 17 of gestation onward. The anti-CR3 mAb 5C6 was used to investigate the role of CR3 in adhesion, spreading, and phagocytosis by neonatal Mphi. Neonatal macrophages were found to adhere, spread, and phagocytose by CR3-dependent mechanisms, and a CR3-independent system was implicated in the spreading of neonatal Mphi. The role of CR3 in migration during development was then investigated. 5C6 had potent effects on the early stages of the migration of myelomonocytic cells to an inflammatory stimulus in vivo. Despite efficient transplacental transfer of the Ab from pregnant mother to fetus, the process by which monocytes generate populations of resident tissue Mphi was undisrupted, indicating the existence of CR3-independent mechanisms of monocyte migration during development.

Animals↗
PubMed1998

Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease.

Macrophage scavenger receptors (MSR) are implicated in the development of atherosclerosis and amyloid b-protein deposition in Alzheimer's disease. However, histopathological studies of MSR expression in human tissues have been hampered by a lack of specific antibodies. Using MSR-deficient mice, we successfully raised a novel monoclonal antibody against human MSR together with high-titer antisera. These antibodies specifically recognized human tissue macrophages and human MSR protein purified from differentiated THP1 cells. In normal brain, MSR staining was mainly distributed to the perivascular cells, which correspond to Mato's fluorescent granular perithelial cells (Mato cells). In the lesions of ischemia and Alzheimer's disease, a subset of microglia stained positive for MSR. These novel antibodies are useful tools for analysis of MSR expression in human tissues.

Alzheimer Disease↗
PubMed1998

Lack of p56lck expression correlates with CD4 endocytosis in primary lymphoid and myeloid cells.

In cell lines the endocytic properties of CD4 are regulated through its association with the src-family tyrosine kinase p56lck. In lymphoid cell lines expressing p56lck, CD4 is restricted to the cell surface and undergoes only limited internalization. Phosphorylation of the cytoplasmic domain of CD4 causes p56lck to dissociate and activates an endocytosis signal leading to the internalization of CD4 through clathrin-coated pits. In p56lck-negative transfected cell lines CD4 is constitutively internalized, but internalization is inhibited when p56lck is expressed in these cells. We now demonstrate that these endocytic properties of CD4 determined in transfected cell lines hold true for CD4 naturally expressed on myeloid cell lines (HL-60 and U937), as well as on primary lymphocytes, monocytes and macrophages isolated from human blood. CD4 showed limited internalization on p56lck-positive lymphocytes, but was rapidly internalized in p56lck-negative monocytes and macrophages. Surprisingly, rapid internalization of CD4 was seen with the lymphocytes from one unidentified donor. In these cells we failed to detect p56lck expression by Western blotting.

Animals↗
PubMed1998

Myeloid-specific gene expression.

The mononuclear phagocytes are recruited from bone marrow precursors to most tissues of the body, particularly during inflammation or immune stimulation. This combination of accessibility as stem cells and heterogenity of tissue locations makes the myeloid cell potentially important as a carrier of therapeutic agents. Understanding the regulation of transcription in myeloid cells is necessary for any future design of tissue-specific gene targeting vectors, particularly if there are inherent size limitations. Identified members of the C/EBP, Runt/PEBP2/CBF, and Ets families of transcription factors are critical for myeloid-specific gene expression and may have myeloid-restricted expression or myeloid-specific regulation in the hematopoietic system. AP-1, Sp1, and Myb appear to be important for myeloid-restricted expression in some cases. In addition, factors involved in the up-regulation of the level of gene expression when macrophages are activated by agents such as interferon-gamma and bacterial products have been identified. Some of the sequences to which these transcription factors bind in myeloid-restricted genes have been tested in cell lines and in transgenic mice and it is now possible to make an attempt to describe the characteristics of a myeloid-specific promoter.

Animals↗
PubMed1998

The EGF-TM7 family: unusual structures at the leukocyte surface.

The isolation of cDNA clones encoding mouse F4/80, human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 1 (EMR1) and human CD97 has resulted in the description of a novel family of seven-transmembrane spanning cell surface molecules. These members of the EGF-TM7 family are characterized by a variable number of NH2-terminal EGF domains and seven transmembrane-spanning hydrophobic regions, which demonstrate a degree of sequence homology to the corresponding region in members of the G-protein-coupled peptide hormone receptor family. The F4/80 molecule is macrophage-restricted, as determined by immunohistochemical analysis of a wide range mouse tissues, while mRNA transcripts encoding EMR1, the predicted human F4/80 homologue, also appear to be abundantly expressed by cells of the myelomonocytic lineage. CD97, for which a cellular ligand has been identified (CD55), is expressed on a diverse array of leukocytes and is markedly upregulated on activated T and B cells. The regulation of expression of the EGF-TM7 genes, the physiologic function(s) of these novel receptors and the further identification of their ligands is the subject of both intense study and this review.

Animals↗
PubMed1998

Oral trovafloxacin compared with intravenous cefoxitin in the prevention of bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease. Trovafloxacin Surgical Group.

BACKGROUND: Trovafloxacin is a new fourth-generation fluoroquinolone whose pharmacokinetics and in vitro activity suggest that it is well suited for antibiotic prophylaxis in elective hysterectomy. METHODS: In a randomized, double-blind, multicenter study, parallel groups of women 18 years of age or older received either 200 mg trovafloxacin by mouth and intravenous (i.v.) placebo or 2 g cefoxitin by i.v. infusion and placebo by mouth before elective vaginal or abdominal hysterectomy for nonmalignant disease. RESULTS: In the 103 and 97 patients in the trovafloxacin and cefoxitin groups, respectively, who were evaluable for efficacy, the prophylactic success rates at hospital discharge (96% in both groups) and 30 +/- 6 days after hysterectomy (88% and 91% in the trovafloxacin and cefoxitin groups, respectively) were statistically equivalent. Both antibiotics were well tolerated. CONCLUSION: A single oral 200 mg dose of trovafloxacin is as effective and safe as a standard cefoxitin parenteral regimen in the prevention of primary bacterial infection after elective vaginal or abdominal hysterectomy for nonmalignant disease.

Administration, Oral↗
PubMed1998

Recognizing death: the phagocytosis of apoptotic cells.

Although apoptotic cell death is widespread, dying cells are rarely seen in situ because of their rapid clearance by neighbouring phagocytes. Phagocytic recognition of apoptotic cells is less well understood than the death programme itself, but an increasing number of recent studies are highlighting its importance. This review discusses the nature of the receptors that have been implicated in apoptotic cell phagocytosis, the mechanisms of uptake and the immunological consequences of apoptotic cell ingestion.

Animals↗
PubMed1998

Scavenger receptors: diverse activities and promiscuous binding of polyanionic ligands.

Scavenger receptors are a diverse family of proteins that share a common property--the binding of modified lipoprotein--but they have recently been shown to recognise a diverse range of ligands. Understanding the molecular interaction of receptor-ligand binding should provide insight into how scavenger receptors contribute to important biological processes.

Amino Acid Sequence↗
PubMed1998

Recent progress in defining the role of scavenger receptors in lipid transport, atherosclerosis and host defence.

Scavenger receptors bind and internalize modified lipoproteins. There are several different classes of scavenger receptors in mammalian cells and their relative contribution to lipid transport in normal physiology and pathological conditions such as atherosclerosis has been the subject of intense investigation. Mice with a disruption in the macrophage scavenger receptor SR-A gene exhibit a reduced size of atherosclerotic lesions and also exhibit an enhanced susceptibility to pathogens and endotoxic shock. In addition to their role in lipid transport, scavenger receptors play important roles in host defence and in the regulation of acquired immunity. Recent progress in delineating the mechanisms by which oxidized LDL effects changes in gene expression will be reviewed.

Animals↗