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PubMed2002

Time course of the development of Alzheimer-like pathology in the doubly transgenic PS1+APP mouse.

Doubly transgenic mice expressing both a mutated amyloid precursor protein and a mutated presenilin-1 protein accumulate A(beta) deposits as they age. The early A(beta) deposits were found to be primarily composed of fibrillar A(beta) and resembled compact amyloid plaques. As the mice aged, nonfibrillar A(beta) deposits increased in number and spread to regions not typically associated with amyloid plaques in Alzheimer's disease. The fibrillar, amyloid-containing deposits remained restricted to cortical and hippocampal structures and did not increase substantially beyond the 12-month time point. Even at early time points, the fibrillar deposits were associated with dystrophic neurites and activated astrocytes expressing elevated levels of glial fibrillary acidic protein. Microglia similarly demonstrated increased staining for complement receptor-3 in the vicinity of A(beta) deposits at early time points. However, when MHC-II staining was used to assess the degree of microglial activation, full activation was not detected until mice were 12 months or older. Overall, the regional pattern of A(beta) staining resembles that found in Alzheimer disease; however, a progression from diffuse A(beta) to more compact amyloid deposits is not observed in the mouse model. It is noted that the activation of microglia at 12 months is coincident with the apparent stabilization of fibrillar A(beta) deposits, raising the possibility that activated microglia might clear fibrillar A(beta) deposits at a rate similar to their rate of formation, thereby establishing a relatively steady-state level of amyloid-containing deposits.

Aging↗
PubMed1996

Assessment of protein fold predictions from sequence information: the predicted alpha/beta doubly wound fold of the von Willebrand factor type A domain is similar to its crystal structure.

The fold of the von Willebrand Factor type A domain (vWF-A) was predicted to be similar to an alpha/beta doubly wound fold in the GTP-binding domain of ras-p21, despite the lack of sequence or functional similarity. This was subsequently confirmed by the vWF-A crystal structure from complement receptor type 3. The prediction is now reviewed. The vWF-A secondary structure was predicted with 62 to 75% accuracy and 12 of the 13 secondary structure elements were identified correctly. Accessibility predictions were 69 to 71% accurate. The fold recognition analysis was confirmed, but was much improved by averaging the results from 70 complete vWF-A sequences. The related folds of ras-P21 and flavodoxin scored highly. In addition, both the mapping of the predicted vWF-A secondary structure elements with those in 12 known alpha/beta folds and two Asp residues at the C-terminal ends of two adjacent beta-strands matched well with ras-p21 and flavodoxin. The predicted Mg(2+)-binding site, two disulphide bridges and the secondary structure topology were largely accurate. The exception is the reversal of a beta-hairpin at one end of the central beta-sheet. We conclude that non-homologous folds with dissimilar functions can be predicted from sequence data with reasonable accuracy, and that the accuracy in this case was principally limited at the periphery of the fold.

Amino Acid Sequence↗
PubMed1997

Differential effects on HIV-1 gene regulation by EBV in T lymphocytic and promonocytic cells transduced to express recombinant human CR2.

A panel of human hematopoietic cell lines was genetically engineered to express recombinant complement receptor 2 (CR2 or CD21), which is also the Epstein-Barr virus (EBV) receptor. The panel was composed of SupT1, J1.1, and U1.HIV cells. The latter is a promonocytic cell line, whereas the other two are T lymphocytic cell lines. J1.1 and U1.HIV cells are latently infected by human immunodeficiency virus type 1 (HIV-1). These three cell lines were transduced with a murine leukemia virus (MLV)-based retroviral vector system. CR2 was efficiently and consistently expressed on the cell membranes, conferring enhanced susceptibility to EBV infection. The efficient expression of recombinant CR2 in cell lines of hematopoietic origin allowed for study of the interaction between EBV infection and HIV-1 gene regulation in suitable cell-culture models. The effects of EBV and HIV-1 coinfection results were cell-type dependent. In the two T lymphocytic cell lines, HIV-1 expression was rapidly and persistently down-regulated by EBV. Conversely, in the promonocytic cell line U1.HIV-CR2, HIV-1 expression was transiently enhanced by EBV. The EBV and HIV-1 coinfection result in U1.HIV-CR2 cells is potentially important, as the activation of HIV-1 gene expression in monocyte-like cells may play a crucial role in the mechanism of CD4+ T cell depletion by apoptosis. Therefore, the U1.HIV-CR2 cell line may represent a useful cell-culture system to study the synergism between EBV and HIV-1 in inducing apoptosis in primary CD4+ T cells.

Cell Line↗
PubMed1994

Expression of major histocompatibility complex class II antigen on amoeboid microglial cells in early postnatal rat brain following intraperitoneal injections of lipopolysaccharide.

In rats given two single intraperitoneal injections of lipopolysaccharide (LPS) at 1 and 4 days of age and killed at 7 days of age, 11.5--12% of amoeboid microglial cells (AMC) in the supraventricular corpus callosum were induced to express major histocompatibility complex (MHC) class II antigen, as detected with monoclonal antibody OX-6. The MHC class II antigen induced was colocalized with MHC class I antigen and type 3 complement receptors on the same cells. The expression of MHC class II antigen on the plasma membrane of AMC was confirmed in immunoelectron microscopy. Although OX-6-positive AMC often assumed a perivascular position, the majority of them, however, were far removed from the blood vessels. The cytoplasmic processes of the perivascular OX-6-positive AMC appeared to rest directly on the vascular lamina, and in some section profiles they were in contact with a large surface area of the outer wall of small blood vessels. It is concluded from this study that although MHC class II antigen is not constitutively present on AMC, it is, however, inducible under stimulation with LPS. It is, therefore, suggested that the OX-6-positive AMC, especially the perivascular AMC, may have the potentiality to function as antigen-presenting cells in the developing brain when challenged by LPS.

Animals↗
PubMed1985

The expression of Ia-antigen on nasopharyngeal carcinomas xenografted into nude mice.

The expression of Ia-antigen on four different Epstein-Barr virus associated nasopharyngeal carcinomas xenografted into athymic mice could be detected by the monoclonal antibody OKIa. Xenografts of four additional head and neck tumors other than nasopharyngeal carcinoma and one xenograft of a metastatic melanoma cell line were negative for the Ia-antigen. Control antibodies OKT3, OKT4, OKT9, OKM1 and Leu7 were negative with all nasopharyngeal carcinomas and the non-nasopharyngeal carcinoma xenografts. Complement receptors as the presumed receptors for the Epstein-Barr virus could not be detected on xenografted nasopharyngeal carcinoma cells but were found on freshly prepared peripheral blood lymphocytes as well as on the Epstein-Barr virus transformed lymphoblastoid cell line QIMR-WIL. The possible role of the Ia-antigen on nasopharyngeal carcinoma cells in respect to the Epstein-Barr virus association of this malignancy is discussed.

Animals↗
PubMed1996

Urocanic acid suppresses the activation of human neutrophils in vitro.

Exposure to ultraviolet (UV) light impairs the function of inflammatory cells. Urocanic acid (UCA) in an stratum corneum has been suggested as a mediator in the immunosuppression of lymphoid cells detected after irradiation with UVB (UV wavelengths 280-320 nm). In this study, we examined the effects of the two UCA isomers, trans and cis UCA on human polymorphonuclear leukocytes, neutrophils. It was found that treatment of cells with either trans of cis UCA isomers inhibited the opsonized zymosan-induced respiratory burst activity, measured with luminol-enhanced chemiluminescence assay. Both isomers were also able to partially block the up-regulation of complement receptors 1 (CR1; CD35) and 3 (CR3; CD11b/ CD18) in N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils. These results indicate that the isomerization of trans UCA to cis UCA is not essential for the action of UCA on neutrophils. Neither of the UCA isomers were found to induce cyclic AMP (cAMP) formation in 3-isobutyl-1-methylxanthine treated cells, suggesting that the activation of adenylate cyclase cAMP system is not involved in UCA provoked suppression of neutrophils. It is concluded that the function of UCA may be protective, to suppress the activation of human neutrophils in inflamed, sunburned epidermis.

Cyclic AMP↗
PubMed1991

New insights into mechanisms of oxyradical and neutrophil mediated lung injury.

Acute lung injury in rats developing after systemic complement activation or deposition of IgG immune complexes is complement-dependent and oxygen radical-mediated. Recent findings have shown that a soluble complement receptor (sCR1) is capable of attenuating injury. Additional studies have also demonstrated requirements for the cytokines, TNF alpha, and for L-arginine derived products in lung injury that follows deposition of IgG immune complexes.

Animals↗
PubMed2000

Microglial and astrocytic reactions prior to onset of thalamic cell death after traumatic lesion of the rat sensorimotor cortex.

The temporospatial relationship between microglial and astrocytic reactions and delayed thalamic cell death was examined 1-7 days following a traumatic cold lesion of the rat sensorimotor cortex using immunocytochemistry in combination with terminal deoxynucleotidyltransferase-mediated biotinylated dUTP nick end labeling (TUNEL) of nuclear DNA fragmentation. No or only occasional TUNEL-positive cells were found in the thalamic relay nuclei up to 3 days after trauma. After 7 days, on the other hand, a considerable number of TUNEL-positive cells were seen in the ventrobasal, the ventrolateral and posterior thalamic nuclei. Already 3 days after trauma, i.e., before cell injury was detectable, many protoplasmic astrocytes, which were reactive for glial fibrillary acidic protein, and ramified microglia, which were positive for complement receptor type 3b (CR3b) but negative for major histocompatibility complex (MHC) class II antigen, were noticed in the thalamus. The number of labeled astro- and microglia further increased after 7 days, when DNA fragmentation became evident. At this time, the morphology of microglia shifted towards bushy and rod-like cells, and microglia became also reactive for MHC class II antigen. Clusters of CR3b- and MHC class II-positive microglia were found in the ventrobasal thalamus. The present findings demonstrate that trauma-induced microglial and astrocytic reactions appear in the thalamus prior the onset of cell damage.

Animals↗
PubMed1998

Interleukin-13 increases prostaglandin E2 (PGE2) production by normal human polymorphonuclear neutrophils by enhancing cyclooxygenase 2 (COX-2) gene expression.

OBJECTIVE: To investigate whether interleukin-13 (IL-13) can affect arachidonic acid metabolism and phagocytic activity of normal human polymorphonuclear neutrophils (PMN). METHODS: Normal human PMN (1 x 10(6) cells/ml) were incubated with different concentrations of IL-13 (0.1-10 ng/ml) for a variety of times (30-120 min). Phagocytosis and intracellular cyclooxygenase-2 (COX-2) were detected by flow cytometry. The expression of COX-1 and COX-2 mRNA was detected by RT-PCR. The concentration of PGE2 in the PMN cultured supernatants was determined by EIA. RESULTS: We found that IL-13 at an optimal concentration of 1 ng/ml significantly enhanced COX-2 gene expression and PGE2 production (121.57 +/- 22.17 pg/ml in IL-13 stimulation vs. 73.16 +/- 11.72 pg/ml in controls) by PMN. In addition, IL-13 stimulated PMN phagocytosis via increased complement receptor type 1 (CR1) and type 3 (CR3), but not IgG Fcgamma receptor type 3 (FcgammaRIII). The cytoplasmic neutral esterase activity of PMN was also enhanced by IL-13 stimulation for 24 h. CONCLUSIONS: These results suggest that IL-13 can stimulate PMN and modulates the inflammatory reactions via the cyclooxygenase pathway.

Cells, Cultured↗
PubMed1990

Antagonistic and additive effects of IL-4 and interferon-gamma on human monocytes and macrophages: effects on Fc receptors, HLA-D antigens, and superoxide production.

During an immune response a multitude of lymphokines are produced which modulate the function of mononuclear phagocytes. In this study, we investigated possible additive, synergistic, or antagonistic effects of three lymphokines, IL-4 (1-100 U/ml, 0.01-1 ng/ml), interferon-gamma (IFN) (1-100 U/ml) and IL-2 (30-300 U/ml) on Fc receptors (FcR1 and FcR2), complement receptors (CR3 and CR4), and HLA-D antigens (HLA-DR and HLA-DQ) on human monocytes and macrophages. Exposure of monocytes to IL-4 alone resulted in changes in the expression of all these receptors. Both FcR1 and FcR2 were downregulated in a dose-dependent manner while the expression of CR3, CR4, HLA-DR, and HLA-DQ was increased. Antagonistic effects of IL-4 and IFN were observed on FcR1 and FcR2; IL-4-induced downregulation of the FcR1 and FcR2 was inhibited by IFN, and vice versa, IFN-induced upregulation of FcR1 and FcR2 was inhibited by IL-4. Phagocytosis of particulate immune complexes (EAs) as well as production of superoxide (O2-) in response to EAs were inhibited by IL-4, and the inhibition was reversed by IFN. Antagonistic effects of IL-4 and IFN were also observed on CR3 and CR4 expression. Additive effects of IL-4 and IFN were on the other hand seen on HLA-DR and HLA-DQ expression as well as on O2- production in response to stimulation with phorbol ester (PMA). The addition of IL-2 to IL-4 and/or IFN-containing cultures had no further modulatory effect on receptor expression or O2- production. In vitro matured macrophages (M phi) had a similar response pattern to IL-4 and IFN as the freshly isolated monocytes. Alveolar macrophages (AM phi), on the other hand, did not modulate FcR1 and HLA-DQ in response to IL-4, and downregulated FcR2 in response to IFN. Antagonistic effects of the two factors were only seen on CR expression. These results imply that FcR expression and function on monocytes and inflammatory macrophages may be in sensitive balance with the relative concentrations of IL-4 and IFN in the immune environment. FcRs on AM phi are less responsive to modulation by these lymphokines.

HLA-DQ Antigens↗
PubMed1986

Molecular calibration in flow cytometry with sub-attogram detection limit.

A monoclonal antibody to complement receptor type 1 (CR1) has been double labelled with 125iodine and fluorescein isothiocyanate (FITC) and used for parallel radioimmune assay (RIA) and flow cytometric studies. Serial dilutions of the reagent with unlabelled antibody were used to obtain a linear correlation between radioactivity counts and fluorescence over the whole range of labelled antibody molecules bound per cell, namely 700-25,000. This has enabled us to calibrate our flow cytometer in terms of numbers of molecules per channel as opposed to the customary arbitrary fluorescence units. Normal human granulocytes from a single donor were found to have a mean of 25,000 CR1 molecules per cell with a normal distribution and standard deviation of 4775 molecules. The detection limit of the flow cytometer was 730 CR1 molecules per cell which is equivalent to between 125 and 150 molecules of free fluorescein. This represents less than 0.1 attogram (ag) of fluorescein per cell, where 1 ag = 10(-18) g. The resolution was 44 CR1 molecules per digitization step of the analogue-to-digital converters (ADC) which corresponds to the fluorescence from less than ten molecules of free fluorescein.

Calibration↗
PubMed1990

A cell-ELISA for the quantification of adherent murine macrophages and the surface expression of antigens.

The present study was performed in order to establish whether a cell-ELISA could be used to determine the expression of antigens by adherent murine peritoneal macrophages and also quantify the numbers of such macrophages. Accurate determination of the number of adherent macrophages proved to be possible with a cell-ELISA designed to assess complement receptor type III (CRIII) expression. Expression of CRIII was considerably more sensitive than determination of the cell-protein or DNA content as a measure of the number of adherent macrophages. For the calculation of the expression of CRIII, Ia antigen, and antigen F4/80 by resident and activated macrophages, use was made of the linear part of the curve obtained when the numbers of macrophages were plotted against the absorbance values for each of the antigens. The values for CRIII expression did not differ significantly between resident macrophages, macrophages activated with recombinant interferon-gamma (rIFN-gamma) and macrophages activated with BCG/PPD. IFN-gamma-activated and BCG/PPD-activated macrophages expressed Ia antigen significantly more intensely than did resident peritoneal macrophages. In contrast the activated macrophages expressed F4/80 significantly less intensely than resident peritoneal macrophages.

Animals↗
PubMed1989

The effect of tumor necrosis factor-alpha and interferon-gamma on neutrophil function.

Tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma) have been shown to regulate cell-mediated immunity and act as effective modifiers of immune function; however, their influence on neutrophil (PMN) function is not well defined. This study investigated the effect of these cytokines on PMN phagocytosis, respiratory burst, and complement receptor (C3b) expression. Human citrated whole blood was incubated with either phosphate-buffered saline (control), 20 micrograms Escherichia coli lipopolysaccharide (LPS), TNF (1, 10, or 100 units), or IFN-gamma (1, 10, or 100 units). Synergy was also assessed between TNF and IFN-gamma. Phagocytosis and respiratory burst were assayed by sequential incubation of blood with dichlorofluorescein diacetate followed by labeled Staphylococcus aureus. C3b receptor expression was assayed by labeled anti-CR3 monoclonal antibody. Measurements were expressed as the mean channel fluorescence of 2000 PMNs counted by flow cytometry. IFN-gamma alone at all doses had no effect on any of the parameters measured. TNF 1 unit/ml increased phagocytosis (666 +/- 47 vs 542 +/- 19), respiratory burst (326 +/- 33 vs 258 +/- 17), and C3b (374 +/- 42 vs 157 +/- 14; all P less than 0.05) over those of control. TNF also demonstrated dose-dependent PMN activation. The combination of TNF + IFN-gamma increased both respiratory burst and C3b compared to either agent alone. These data indicate that TNF enhances PMN function and cytokine interaction may be important in PMN activation.

Humans↗
PubMed1991

Modulation of human alveolar macrophage properties by ozone exposure in vitro.

We have investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3) (0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2 (PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, we found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2-) production in response to phorbol ester was reduced after exposure of HAM to O3 while the basal O2- release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3- exposed HAM produced significantly lower levels of these cytokines when stimulated with bacterial lipopolysaccharide (LPS). Two-dimensional gel electrophoretic analysis of proteins made by HAM following in vitro exposure to O3 identified 11 proteins whose rate of synthesis was significantly altered. Thus, these studies show that exposure to O3 alters the functional competence of HAM. While there is a minimal effect on protein expression or synthesis, the responses of HAM to particulate immune complexes, to bacterial LPS, and to PMA are impaired. The release of arachidonic acid and PGE2 suggest that the effect of O3 is primarily targeted to the HAM cell membrane. These changes may ultimately result in increased susceptibility to inhaled infectious agents in the O3-exposed individual.

Adult↗
PubMed1983

Fetal and maternal immunologic manifestations of intrauterine Adenovirus SV-20 infection.

Rhesus monkey fetuses of either immune or nonimmune dams were inoculated in utero with Adenovirus SV-20 (AdSV-20), a virus capable of inducing fetal pneumonia, and studied immunologically at various intervals. AdSV-20 infection at 90-100 days gestational age resulted in absolute lymphopenia in a few fetuses, reduced numbers of peripheral blood lymphocytes (PBL) which formed rosettes with sheep erythrocytes (ERL) and reduced complement-receptor lymphocytes (CRL) in a majority, while Fc fragment-receptor lymphocytes (FcRL) were occasionally increased. There was a tendency for depression of ERL and CRL early in infection of 120-130-day fetuses, followed by stimulation of these populations and FcRL in later phases. Maternal immunity did not protect against these effects of AdSV-20 infection in fetuses. Immune and nonimmune dams were spared adverse clinical effects and had no changes in lymphoid cell populations following inoculation of their fetuses. Despite precocious production of circulating IgM, fetuses of nonimmune dams had little or no demonstrable anti-AdSV-20 serum neutralizing (SN) antibody, indicating that the ability to develop an effective immune response was suppressed or had not been acquired at the gestational ages studied. Nonimmune dams displayed little evidence of seroconversion following inoculation of their fetuses with AdSV-20, except in those dams whose fetuses died in utero, whereby there was a significant antibody response. SN antibody titers of immune dams were not boostered substantially subsequent to inoculation of their fetuses, and fetal SN titers were lower than maternal titers, suggesting absence of an active fetal antibody response in this group also. Direct inoculation of AdSV-20 into 90-130-day rhesus monkey fetuses provided a model system for immunologic study of fetal infection, probably involving complex fetal-maternal interactions, in a situation where the infected, viable fetus and its dam appeared to be microbiologically isolated from one another.

Adenoviruses, Simian↗
PubMed1992

Density separation of human red blood cells on self forming Percoll gradients: correlation with cell age.

Human red blood cells were density separated on self-forming Percoll gradients. Redistribution of density fractionated red blood cells was studied by recentrifugation on self-forming Percoll gradients. A protocol that avoids centrifugation of red cells prior to removal of white cells and introduces EDTA before red cell pelleting completely avoided redistribution. Dense red cells separated according to this method were senescent on the basis of a biochemical and a physical criterion: the increase in the band 4.1a:4.1b ratio (Mueller, T., Jackson, C.W., Dockter, M.E. and Morrison, M. (1987) J. Clin. Invest. 79, 492-499) and the loss of maximum deformability. Characterization also included the relative content of two surface proteins (complement receptor 1, CR1 (Ripoche, J. and Sim, R.B. (1986) Biochem. J. 235, 815-821); decay accelerating factor, DAF) on density fractionated red cells. Unlike cytoplasmic proteins, these proteins face similar conditions, whether located on circulating reticulocytes or aging red cells. Both components were lost linearly within experimental errors with cell density and were lower by 60 and 40% in dense than light cells, respectively.

Blood Proteins↗
PubMed1996

Cyclin D1 messenger RNA is induced in microglia rather than neurons following transient forebrain ischaemia.

Following 30 min of forebrain ischaemia in the rat, delayed neuronal death occurs in the CA1 sector of the hippocampus within two to three days, whereas neurons in other selectively vulnerable regions, such as the dorsolateral striatum, die within 6-12 h. In this study, we investigated cyclin D1 expression, which codes for a regulatory protein in cell cycle regulation, but it is also induced in sympathetic neurons undergoing programmed cell death. Cyclin D1 messenger RNA could not be detected by in situ hybridization techniques in brains of control rats, but was found at one and two days after ischaemia in regions of the dorsolateral striatum with neuronal degeneration. DNA fragmentation in this region, identified by the terminal transferase biotinylated-UTP nick end labelling (TUNEL) procedure, was observed from 6 h after ischaemia onward. In the hippocampus, increased levels of cyclin D1 messenger RNA were found at two and three days after ischaemia in the striatum pyramidale of the CA1 sector. This expression was associated with the occurrence of neuronal damage and TUNEL-stained neurons. By seven days cyclin D1 messenger RNA was found in hardly any brain structure. There was no temporospatial overlap of cyclin D1 expression with the expression of the immediate-early genes c-fos, c-jun, and mkp-1, a result which is clearly distinct from findings in sympathetic ganglion neurons undergoing programmed cell death. These results do not suggest a role for cyclin D1 in neuronal cell death following transient forebrain ischaemia. The similarity of the cyclin D1 expression profile with that of the microglia-specific CR3 complement receptor beta-subunit messenger RNA, and the results of combined in situ hybridization and microglia-specific immunohistochemistry suggest that microglia are the source of cyclin D1 messenger RNA in the postischaemic brain. Since cyclin D1 codes for a critical regulatory protein for progression of the G0 to G1 phase in the cell cycle and we did not observe prominent occurrence of DNA fragmentation in microglial cells in the hippocampus at time points when cyclin D1 messenger RNA was found, we suggest that cyclin D1 induction is involved in the onset of microglial cell proliferation.

Animals↗
PubMed2005

Adherence modifies the regulation of gene expression induced by interleukin-10.

Interleukin-10 (IL-10) is a well known anti-inflammatory cytokine. However, we previously showed that it could present pro-inflammatory properties on human monocytes in the absence of adherence. In the present study, using macroarray technology, we analyzed the effects of IL-10 and adherence on the expression of 1050 genes in human monocytes cultured for 3 hours on plastic or Teflon(R) (to avoid adherence). Adherence alone induced specifically the expression of 12 genes and repressed that of 25 genes. In adherent monocytes, IL-10 induced the expression of 21 genes and repressed that of 50 genes. In non-adherent monocytes, IL-10 induced the expression of 45 genes and repressed that of 67. Only 3 common genes were induced while 35 common genes were repressed by IL-10 in the two culture conditions. Interestingly, we showed that IL-10 modulated conversely on Teflon(R) and plastic the expression of 16 genes, of which SOCS molecules, coproporphyrinogen oxidase, matrix metalloproteinases and complement receptor-1 (CD35). This study demonstrates that adherence has profound modulatory effects on the properties and the signaling induced by IL-10. The discovery that IL-10 can inhibit the production of coproporphyrinogen oxidase (an enzyme involved in the synthesis of heme) may shed some lights on the mechanisms of anaemia induced by IL-10. Furthermore, the inhibition of the expression of SOCS1 by IL-10 in the absence of adherence, may explain its priming effects on a subsequent LPS stimulation that we previously described.

Cell Adhesion↗