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S Gordon

Publications and source records attributed to S Gordon.

At least 19 recordsLinked to original sources
PubMed1992

Interleukin 4 regulates induction of sialoadhesin, the macrophage sialic acid-specific receptor.

Sialoadhesin is a nonphagocytic lectin-like receptor found on a restricted population of tissue macrophages in lymphoid and hemopoietic tissues. In bone marrow, it is localized to areas of contact between the resident stromal macrophages and developing granulocytes, which together form myeloblastic clusters. Sialoadhesin is highly specific for sialylated glycoconjugates and may play a role in adhesion and trophic hemopoietic cell interactions, although its function is unknown. Resident peritoneal macrophages do not express high levels of sialoadhesin in vitro unless an inducing element found in normal mouse serum is present. The restricted in vivo location of this marker and its induction by mouse serum prompted us to examine the possible influence of various cytokines on its expression, measured by a sheep erythrocyte rosetting assay. None of the cytokines tested was able to induce sialoadhesin; however, interleukin 4 (IL-4) prevented the induction in the presence of serum. Expression of other macrophage markers was not influenced in parallel, and Western blotting showed that sialoadhesin antigen in cell lysates was selectively reduced by IL-4. Inhibition by IL-4 was dose dependent, could be blocked by antibodies to both IL-4 and the IL-4 receptor, and was overcome by increased serum concentrations. IL-4 is therefore a potent cytokine regulator of the sialic acid-specific receptor implicated in macrophage-hemopoietic cell interactions.

Animals↗
PubMed1992

Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system.

Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium.

Animals↗
PubMed1992

Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation.

Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN-gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion.

Animals↗
PubMed1992

Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system constitutively express major histocompatibility class II antigens.

Using immunocytochemistry we have shown that there is a population of macrophages within the stroma of the choroid plexus of rats and mice which expresses high levels of major histocompatibility complex Class II antigens. In whole mount preparations of the choroid plexus, the morphology and regular distribution of these cells is similar to the Langerhans cells of the skin. These cells reside at an important interface between the central nervous system and the peripheral immune system and their possible role in immune-mediated diseases of the central nervous system is discussed.

Animals↗
PubMed1992

The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues.

Acute inflammation is important for defence against infection, wound repair and the mediation of auto-immune tissue destruction. Myelomonocytic recruitment in acute inflammation is a stereotyped and non-specific response to tissue insult which begins within 2 h. In this study, lipopolysaccharide was injected into the murine CNS and other body sites of mice to compare the inflammatory responses. Doses of lipopolysaccharide which induced typical myelomonocytic recruitment in skin and the choroid plexus had no effect in CNS parenchyma, apart from the morphological activation of local resident microglia. The CNS parenchymal response proceeded independently of that in the choroid plexus-cerebral ventricles and had three distinct and unique phases. Initially there was minimal neutrophil exudation and a two-day delay before any increase in macrophage-microglial cell number. Next, there was a rapid increase in macrophage-microglial cell numbers during the third day, mainly due to recruitment of blood monocytes. During this phase, leukocyte recruitment was restricted to monocytes which rapidly adopted the arborized microglial phenotype. Monocytes migrated through an intact blood-brain barrier independent of changes in solute permeability. Finally, there was a florid myelomonocytic reaction predominantly in the white matter, one week after intracerebral injection of 2 micrograms lipopolysaccharide. At this time, the leukocyte reaction disrupted the blood-brain barrier, mononuclear phagocytes expressed macrophage morphology and abundant major histocompatibility complex Class II antigen, and T lymphocytes were present. Myelomonocytic entry into the CNS was partially inhibited by prior blockade of the type 3 complement receptor, known to mediate leukocyte adhesion to endothelium elsewhere. The processes which lead to rapid myelomonocytic recruitment in other tissues are absent in CNS parenchyma. Understanding the molecular mechanisms responsible could have considerable significance both for CNS pathophysiology as well as possible anti-inflammatory therapeutic application elsewhere in the body.

Animals↗
PubMed1992

Turnover of resident microglia in the normal adult mouse brain.

We undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [3H]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 +/- 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 +/- 0.052%. From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: (i) resident microglia can synthesise DNA and go on to divide in situ; (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia.

Animals↗
PubMed1992

Macrophages in tissues and in vitro.

Macrophages have specialized functions in different tissue microenvironments such as lymphohaemopoietic organs and the nervous system. Recently, progress has been made in defining cellular and molecular properties of isolated and tissue macrophages in the developing and adult animal.

Animals↗
PubMed1992

Immunocytochemical characterization of the endocytic and phagolysosomal compartments in peritoneal macrophages.

We have used endocytic and phagocytic tracers in an EM immunocytochemical study to define the compartments of the phagocytic and endocytic pathways in mouse peritoneal macrophages. Endocytosed BSA-gold appeared successively in early endosomes, spherical endosomal vesicles, a late endosomal tubuloreticular compartment (TC), and terminal lysosomes. The TC appeared as an elaborate structure enriched for the lysosomal membrane glycoproteins Lamp 1 and Lamp 2, and expressing significant levels of rab7, a late endosome-specific GTP-binding protein. The cation-independent mannose-6-phosphate receptor was restricted to specialized regions of the TC that were predominantly adjacent to the Golgi complex. Both the early endosome and the TC had coated bud structures whose composition and function are presently unknown. Phagolysosomes containing latex beads expressed the same membrane antigens and received endocytic tracers simultaneously with the TC. Since the membrane surrounding both organelles was also in direct continuity, we assume that both structures form one functional compartment. Macrosialin, an antigen confined to macrophages and dendritic cells, was heavily expressed in TC and phagolysosomal membranes with low levels being detected in other endosomal compartments and on the cell surface. Treatment of cells with wheat germ agglutinin drastically altered the morphology of the TC, giving rise to sheets of tightly adherent membrane and greatly expanded vesicles, in which cell-associated wheat germ agglutinin was concentrated. The spherical endosomal carrier vesicles loaded with internalized gold tracers clustered nearby, often making contact without fusing. Since the delivery of endocytic tracer to the TC was significantly delayed these experiments suggest that the lectin is somehow preventing the endosome vesicles from fusing with the TC. Collectively, our data argue first that the PLC is equivalent to the "tubular lysosomes" commonly described in macrophages, and second that the meeting of the phagocytic and endocytic pathway occurs in this compartment.

Animals↗
PubMed1992

Comparison of allergic responses to dust mites in U.K. bakery workers and Swedish farmers.

The IgE RAST response to Dermatophagoides pteronyssinus and four storage mites (Lepidoglyphus destructor, Tyrophagus putrescentiae, Glycyphaghus domesticus, and Acarus siro) was examined in 251 U.K. bakery workers and compared with that previously found in 440 Swedish farmers. Storage mites are found commonly in stored hay and grain so both these groups potentially encounter them in their work. In neither group of workers was a positive RAST (greater than or equal to 0.35 PRU) to D. pteronyssinus correlated with a positive RAST to a single storage mite. As in the Swedish farmers, significant though not strong correlations were found in the U.K. bakers between positive RAST responses to G. domesticus and L. destructor and to T. putrescentiae and L. destructor (P less than 0.05). Homologous and heterologous RAST inhibition studies showed there was low cross-reactivity between storage mites and D. pteronyssinus. L. destructor showed the least inhibition by the other antigens, suggesting it possessed the fewest common allergens. The most important difference in the IgE responses between the two groups was the much higher response to D. pteronyssinus in the U.K. bakers, which was not found in the Swedish farmers whose highest IgE response was to L. destructor.

Agriculture↗
PubMed1992

Antimicrobial susceptibility patterns of common and unusual species of enterococci causing infections in the United States. Enterococcal Study Group.

We collected 705 isolates of enterococci (1 per patient) from cultures of a variety of anatomic sites from patients at eight tertiary-care hospitals in six geographic regions of the United States. A total of 632 (90%) Enterococcus faecalis, 58 (8%) E. faecium, 5 E. gallinarum, 4 E. avium, 3 E. casseliflavus, 1 E. raffinosus, and 1 E. hirae isolate and 1 biochemical variant of E. faecalis were identified; 606 (86%) of these isolates were associated with clinical infections. The most common sites of isolation were the urinary tract (402 [57%]), nonsurgical wounds (94 [13%]), the bloodstream (74 [10%]), and surgical wounds (62 [9%]). High-level resistance to gentamicin or streptomycin or both was detected in 265 (38%) of the isolates. We identified two E. faecalis isolates resistant to vancomycin (MICs, 32 and 128 micrograms/ml) and 11 beta-lactamase-producing E. faecalis isolates. E. faecium isolates were significantly more resistant than E. faecalis isolates to penicillin, ampicillin, piperacillin, imipenem, and ciprofloxacin (P less than 0.001). The MICs for the 15 non-E. faecalis, non-E. faecium enterococci indicated variable resistance to ciprofloxacin and the penicillins. Antimicrobial susceptibility patterns vary among species of enterococci, and these organisms, while commonly resistant to high-level aminoglycosides, can also acquire resistance to vancomycin or the ability to produce beta-lactamase. Because of these diverse antimicrobial resistance mechanisms, successful treatment and control of enterococcal infections with current antimicrobial agents are becoming increasingly difficult.

Adolescent↗
PubMed1992

Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation.

In situ hybridisation has been used to detect mRNAs to the macrophage secretory products, lysozyme, interleukin 1 beta and tumour necrosis factor-alpha. Sections of paraformaldehyde fixed, frozen colonoscopic biopsies from patients with ulcerative colitis, Crohn's disease or normal controls were hybridised with specific radiolabelled probes and the signal detected by autoradiography. Lysozyme mRNA expression was more common in ulcerative colitis (22/27) and Crohn's disease (eight of eight) compared with controls (17/27). Positive cells were found mainly in the subepithelial region in normal colon, while in inflammatory bowel disease they also appeared in the deeper lamina propria. Immunocytochemistry in parallel sections showed that lysozyme mRNA was expressed only in macrophages or in metaplastic Paneth cells in longstanding inflammatory bowel disease. Tissue neutrophils did not express the lysozyme mRNA, though they have large stores of the protein. Tumour necrosis factor mRNA was detected in four of nine controls compared with 11/15 inflammatory bowel disease patients. For interleukin 1 beta, three of eight controls were positive compared with 10/13 with ulcerative colitis. The tumour necrosis factor signal was located mainly in the deeper lamina propria whereas the interleukin 1 beta was seen in subepithelial macrophages. These results confirm increased macrophage activation in inflammatory bowel disease and suggest functional heterogeneity within the intestinal macrophage population.

Adult↗
PubMed1992

Reduction of airborne allergenic urinary proteins from laboratory rats.

Allergy and asthma caused by proteins of laboratory animals, particularly rats and mice, are the most important occupational health hazards for the scientists and technicians who work with such animals. The influence of different cage litters, cage design, and stock density on measured rat urinary aeroallergen (RUA) concentrations has been examined in a room housing male rats, to determine practical means to reduce allergen concentration in animal laboratories. Eight hour static air samples were taken at 2 1/min and the RUA concentrations measured by radioallergosorbent test (RAST) inhibition. High RUA concentrations occurred when the animals were housed on wood based, contact litter (geometric mean (GM) sawdust 7.79 micrograms/m3; woodchip 6.16 micrograms/m3). The use of noncontact absorbent pads was associated with a significant decrease in RUA concentrations (GM 2.47 micrograms/m3; p less than 0.0001). Rat urinary aeroallergen concentrations fell more than fourfold when the animals were housed on woodbased, contact litter in filter top cages rather than conventional open top cages (GM filter top 0.33 micrograms/m3; open top 1.43 micrograms/m3; p less than 0.0001). The number of rats (stock density) strongly influenced the RUA concentration and a linear relation was found between the log(e) allergen concentration and stock density under these study conditions. The measurement of airborne particle size on cleaning out days showed that all litter types generated similar sized particles: more than 80% of the RUA was carried on particles larger than 8 microns in diameter for all litter types. The findings suggest that the exposure of animal husbandry personnel to RUA may be substantially reduced by the avoidance of contact litter, the use of filter top cages (where suitable), and by keeping stock density to a minimum.

Air↗
PubMed1992

Immune response to flour and dust mites in a United Kingdom bakery.

In a study of 279 United Kingdom bakery workers a high prevalence of immunological response to storage mites was found. To determine whether this was the consequence of exposure to storage mites in bakery work, a population of salt packing workers was examined as a comparison group not at occupational risk of exposure to storage mites. Forty two per cent of both groups were atopic (had a positive skin prick response greater than negative controls to D pteronyssinus, grass pollen, or cat fur by 2 mm or more) and 33% had an immediate skin prick test response to at least one of four storage mites (L destructor, G domesticus, T putrescentiae, A Siro). A higher percentage of the salt packing workers than the bakery workers had a positive radioallergosorbent test (RAST) (greater than or equal to 0.35 PRU) to D pteronyssinus and to the four storage mites. Logistic regression analysis identified atopy as the most significant variable for a positive skin test and RAST response to storage mites in both groups of workers. RAST inhibition was used to analyse extracted area and personal air samples. Analysis of static area samples for aeroallergen showed immunological identity with flour but L destructor was found in only one of seven exposed filters. The concentration of airborne flour was related to exposure rank of perceived dustiness and gravimetric measurement of total dust. Nineteen out of 32 filters from workers in jobs with higher dust exposure (rank >/=6) had a level of > 10 microgram/m(3) flour whereas this concentrations was exceeded in only one of 23 filters from workers in low dust exposure (< rank 6). It is concluded that storage mites are not of special significance in allergic responses in bakery workers. The development of immunological (and airway) responsiveness to inhaled flour dust is increased in those exposed to higher concentrations of airborne allergen, which appears to be predominantly flour and not storage mites.

Air Pollutants, Occupational↗
PubMed1992

Developmental regulation of sialoadhesin (sheep erythrocyte receptor), a macrophage-cell interaction molecule expressed in lymphohemopoietic tissues.

Stromal macrophages in lymphohemopoietic tissues express novel macrophage-restricted plasma membrane receptors involved in nonphagocytic interactions with other hemopoietic cells. One such receptor with lectinlike specificity for sialylated glycoconjugates on sheep erythrocytes and murine hemopoietic cells has been characterized immunochemically and termed sialoadhesin. We have examined sialoadhesin expression during mouse development to learn more about its regulation and function. Immunocytochemical, rosetting, and Western blot studies show that sialoadhesin is first detected on fetal liver macrophages on day 18 of development, 7 days after numerous F4/80+ macrophages are found within erythroblastic islands. In spleen and bone marrow, sialoadhesin appears between day 18 and birth, in parallel with myeloid development. Strongly labeled macrophages in the marginal zone of spleen, characteristic of adult lymphoid tissues, appeared gradually between 1-4 weeks after birth, as the white pulp became enlarged. Isolation of fetal liver macrophages at day 14 confirmed that sialoadhesin was not involved in the binding of erythroblasts, which is mediated by a distinct cation-dependent receptor (Morris et al., 1988, p. 649). Sialoadhesin could be expressed by isolated fetal liver macrophages after cultivation in adult mouse serum, a known source of inducer activity, but was not dependent on the presence of this inducer, unlike adult-derived macrophages. Fetal plasma contained inducing activity on day 13, but adult levels were not reached until 2 weeks postnatally. These studies show that sialoadhesin is differentially regulated compared with the erythroblast receptor and F4/80 antigen, that it is not required for fetal erythropoiesis, and that its induction on stromal macrophages is delayed until the onset of myeloid and lymphoid development. Sialoadhesin provides a marker to study maturation and functions of macrophages during ontogeny of the lymphohemopoietic system.

Animals↗
PubMed1992

Phagocytosis of unopsonized Pseudomonas aeruginosa by murine macrophages is a two-step process requiring glucose.

Pseudomonas aeruginosa is an important pulmonary pathogen in cystic fibrosis, but the means by which it evades host defenses is understood poorly. Macrophages (M phi) are critical in protecting the lung and mucosal surfaces against infection and may need to perform their functions in the absence of opsonins before the evolution of an inflammatory response. The purpose of the present study was to define factors that regulate the capacity of macrophages to mediate nonopsonic phagocytosis. Phagocytosis of unopsonized P. aeruginosa by murine peritoneal and pulmonary alveolar M phi s was absolutely dependent upon the presence of glucose; only D-mannose could substitute. Glucose-dependent phagocytosis appears to be selective for P. aeruginosa by M phi s; ingestion of unopsonized zymosan, opsonized P. aeruginosa, EIgG, and E (IgM)C occurred in the presence or absence of glucose as did-ingestion of unopsonized P. aeruginosa by polymorphonuclear leukocytes. M phi binding and phagocytosis of unopsonized P. aeruginosa appeared to occur by a mechanism independent of complement receptor 3 and mannose receptors. Phagocytosis of P. aeruginosa killed by tobramycin or Formalin was glucose dependent, suggesting that the glucose exerted its effects on the M phi rather than the bacteria. The predilection of P. aeruginosa for lower airway disease in patients with cystic fibrosis might be explained in part by the unique dependency upon glucose for M phi phagocytosis.

Animals↗
PubMed1992

The blood-brain barrier regulates the expression of a macrophage sialic acid-binding receptor on microglia.

In vitro the expression of a sialic acid-binding receptor on murine macrophages, sialoadhesin, is regulated by exposure to an inducing agent present in serum. We have used immunocytochemistry to examine the macrophage populations of the nervous system in order to test whether this serum inducing agent (SIA) also regulates sialoadhesin expression in vivo and whether plasma proteins may influence the phenotype of macrophages of the nervous system. Microglia, the resident macrophages of the central nervous system, reside behind the blood-brain barrier and do not express sialoadhesin. Microglia and macrophage populations in the cicumventricular organs, choroid plexus and leptomeninges are exposed to plasma proteins and some macrophages express sialoadhesin at these sites. Injury to the CNS, which damages the blood-brain barrier, induces sialoadhesin expression on a proportion of macrophages and microglia within the parenchyma. The expression of sialoadhesin matches the temporal and spatial distribution of the plasma extravasation into the brain parenchyma. These experiments show that exposure to SIA is necessary for sialoadhesin expression and lend further support to the idea that the phenotype of microglia is in part regulated by the presence of the blood-brain barrier.

Animals↗