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I George

Publications and source records attributed to I George.

25 records · Page 2Linked to original sources
PubMed1998

Mucin secretion in inflammatory bowel disease: comparison of a macrophage-derived mucin secretagogue (MMS-68) to conventional secretagogues.

We have described a novel macrophage-derived mucin secretagogue (MMS-68) that mediates mucin secretion in colon cancer cell lines and explants of normal and inflammatory bowel disease (IBD) mucosa. We compared MMS-68 induced mucin release with other known intestinal mucin secretagogues in normal colon explants and in the HT-29 colon cancer cell line, and to study the effects of MMS-68 on mucin release from inflamed and uninflamed ulcerative colitis (UC) and Crohn's disease (CD) mucosa. In normal colonic explants and HT-29 cells, each of the secretagogues including, MMS-68-induced mucin release two- to fivefold more than culture medium alone. In HT-29 cells, MMS-68 plus leukotriene C4 (LTC4) induced a 50% increase in mucin release over either secretagogue alone, and MMS-68 plus platelet-activating factor (PAF) markedly enhanced mucin release by eightfold over either secretagogue. In colonic explants from patients with UC and CD, the mucin release in response to MMS-68 was similar to that of normal colonic explants. Likewise, in isolated epithelial cells from CD and UC (whether involved or uninvolved), MMS-68-induced release was similar to that of epithelial cells isolated from normal colonic mucosa. The number of MMS-68-producing macrophages was lower in uninflamed UC mucosa compared with inflamed UC mucosa and CD mucosa. The mucin secretagogue activity of MMS-68 is comparable to that of other known secretagogues, and PAF can have a synergistic effect on this activity. Whole tissue explants and isolated colonic epithelial cells from patients with IBD respond at least as well as their normal counterparts to MMS-68. MMS-68 may play a role in mucin secretion in normal and inflamed colonic tissue.

Carbachol↗
PubMed1998

Effect of ethanol on monocytic function in human immunodeficiency virus type 1 infection.

We have developed a novel system to study monocytic function after human immunodeficiency virus type 1 (HIV-1) infection by infecting a series of human macrophage hybridoma cell lines with HIV-1. Since ethanol has detrimental effects on immune function, we investigated the effect of ethanol and its metabolites acetaldehyde and acetate on monocytic function by utilizing one human macrophage hybridoma cell line, clone 43, as well as primary monocytes. Pretreatment of clone 43 and primary monocytes with ethanol and its metabolites resulted in diminished accessory cell function for mitogen-, anti-CD3-, and antigen-induced T-cell proliferation. The decreased accessory cell function was associated with reduced interleukin 1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha production with loss of intracellular cytokine and mRNA production and the induction of transforming growth factor beta. In ethanol-, acetaldehyde-, and acetate-treated HIV-1-infected clone 43 cells (43HIV), there was a more rapid loss (3 days after infection) of accessory cell function at a lower infecting dose of HIV-1 than that in untreated 43HIV cells. We also observed a more rapid loss of surface class II antigen expression in the ethanol-, acetaldehyde-, and acetate-treated 43HIV cells, but no change in surface expression of CD80 or CD86. Ethanol-induced impairment of monocytic function may compound the immunologic defects of AIDS, making the infected individual more susceptible to the complications of the disease.

Acetaldehyde↗
PubMed1997

Impaired class II expression and antigen uptake in monocytic cells after HIV-1 infection.

Using the human macrophage hybridoma cell line 43 and primary monocytes, we investigated the regulation of class II expression and intracellular Ag trafficking after HIV-1 infection. The HIV-1-infected human macrophage hybridoma cell line, 43HIV, lost class II Ag expression, as determined by immunofluorescence, immunoprecipitation, and Northern blot analysis, 2 wk after infection. Class II expression could be restored by transfection with the full-length HLA-DR4 cDNA driven by a CMV IE promotor. However, even after transfection, the 43HIV cells were incapable of presenting Ag to MHC-matched Ag-specific T cells. This defect was associated with decreased formation of class II-Ag complexes, and similar findings were observed in primary HIV-1BaL-infected monocytes. We investigated Ag uptake using FITC-labeled tetanus, OVA, and keyhole limpet hemocyanin. There was decreased uptake of all three Ags after HIV-1 infection at different time points after Ag pulsing in the 43HIV cells and in primary HIV-1BaL-infected monocytes. There was colocalization of the FITC-labeled Ags with early (cathepsin D) and late endosomal markers (anti-mannose-6-phosphate receptor), lysosomal markers (CD-63), and acidic compartment markers (3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine) in the uninfected cells, but the level of colocalized Ag was reduced in the 43HIV cells and HIV-1BaL-infected monocytes. Our data suggest that class II expression, formation of class II-Ag complexes, and Ag uptake are impaired in chronically HIV-1-infected monocytic cells, which may contribute to the global immunosuppression observed in AIDS.

Antigen Presentation↗
PubMed1996

Altered cytokine production and accessory cell function after HIV-1 infection.

We investigated cytokine production and accessory cell function in human macrophage hybridoma cell lines and primary monocytes after infection with HIV-1. HIV-1 infection induced IL-10 production in the macrophage hybridoma cell line with loss of IL-12 1 wk after infection. There were also significant increases in production of IL-10 (537 +/- 521 vs 687 +/- 625 pg/ml) while there was a reduction in IL-12 (6.3 +/- 3.1 vs 1.2 +/- 1.0 pg/ml, p = 0.021) in the primary monocytes 5 days after HIV-1 infection. In addition, the hybridoma cell lines and primary monocytes failed to support PHA, Con A, PWM, or anti-CD3- induced T cell proliferation 1 wk after infection. The viability of the T cells cocultured with the HIV-1-infected macrophage cell lines or the primary monocytes as determined by propidium iodide staining was unaltered and there was no increase in apoptosis-specific DNA strand breaks or increased expression of Bcl-2 in the T cells. No soluble suppressor factor was present, since UV-inactivated supernatants from the hybridoma cell line and primary monocytes failed to inhibit mitogen- and anti-CD3-induced T cell proliferation. Early events in T cell activation, including calcium flux and phosphotyrosine kinase activity, were intact in the T cells cocultured with the HIV-1- infected hybridomas and monocytes but there was reduced IL-2 production. Addition of exogenous IL-2 restored the proliferative responses. Taken together, these data suggest that alteration of cytokine production and accessory cell function for mitogens and anti-CD3-induced T cell proliferation independent of induction of apoptosis, suppressor factor production, or inhibition of T cell signaling occurs very early after HIV-1 infection and may contribute to the global immunosuppression observed in AIDS.

Apoptosis↗