Biomedical subjects

A Mikulowska

Publications and source records attributed to A Mikulowska.

13 recordsLinked to original sources

PubMed1999

Anti-CD43 monoclonal antibody L11 blocks migration of T cells to inflamed pancreatic islets and prevents development of diabetes in nonobese diabetic mice.

Nonobese diabetic mice are a well-known model for human insulin-dependent diabetes mellitus. These mice develop autoimmune-mediated inflammation of the pancreatic islets, followed by destruction of the insulin-producing beta cells and development of diabetes. Nonobese diabetic mice also have salivary gland inflammation, and serve as a model for human Sjogren's syndrome. T cells are a prominent component of the inflammatory infiltrate in these sites, and T cell recruitment from the blood is thought to be essential for the initiation and maintenance of pathologic tissue damage. A unique mAb to murine CD43, L11, has recently been shown to block the migration of T cells from blood into organized lymphoid tissues. Here we demonstrate that L11 significantly inhibits T cell migration from blood into inflamed islets and salivary glands. Treatment of nonobese diabetic mice with L11 from 1 to 4 or 8 to 12 wk of age led to significant protection against the development of diabetes. Moreover, protection was long-lived, with decreased incidence of diabetes even months after cessation of Ab administration. When treatment was started at 1 wk of age, L11 inhibited the development of inflammation in pancreatic islets and salivary glands. L11 treatment had no long-term effect on numbers or phenotypes of peripheral lymphocytes. These data indicate that anti-CD43 Abs that block T cell migration may be useful agents for the prevention or treatment of autoimmune diseases including insulin-dependent diabetes mellitus and Sjogren's syndrome.

Adoptive Transfer↗

PubMed1999

L11, a unique anti-CD43 monoclonal antibody, inhibits the adoptive transfer of diabetes and pancreatic islet, salivary gland, and lacrimal gland inflammation in NOD/scid mice.

L11 is an anti-murine CD43 monoclonal antibody that blocks the migration of T cells from blood into lymphoid tissues. We used a T-cell-mediated adoptive transfer model to evaluate the ability of L11 to inhibit inflammation and destruction in extranodal tissues in the nonobese diabetic (NOD) mouse. Splenocytes from diabetic NOD mice were transferred intravenously into NOD/scid mice. The host mice were treated with L11, negative control antibody, or saline for the first 8 days after transfer. L11 treatment significantly delayed the onset of diabetes and inhibited the development of inflammation in pancreatic islets, salivary gland, and lacrimal gland. These results suggest that L11 may be a useful immunotherapeutic tool for the prevention of T-cell-mediated autoimmune diseases.

Adoptive Transfer↗

PubMed1999

Amelioration of type II collagen induced arthritis in rats by treatment with sodium diethyldithiocarbamate.

OBJECTIVE: Sodium diethyldithiocarbamate (Ditiocarb, DDTC), which is used in the treatment of heavy metal poisoning, effectively inhibits NF-kappaB activation and cytokine secretion in vitro. To investigate the antiinflammatory and immunosuppressive potency of DDTC, we examined its influence on the course of collagen induced arthritis in rats. METHODS: Arthritis was induced in female DA rats by injection of rat collagen type II emulsified in incomplete Freund's adjuvant into the tail base. After onset of arthritis, the animals received DDTC or vehicle by intraperitoneal injections or subcutaneous infusion using osmotic pumps. Disulfiram, which is cleaved into DDTC within the gastrointestinal tract, was administered orally via gastric gavage. The course of arthritis was followed by clinical scoring and measurement of joint swelling. RESULTS: Collagen induced arthritis was significantly ameliorated by intraperitoneal injection (2 x 300 mg/kg/day) and subcutaneous infusion (120 mg/kg/day) of DDTC and by enteral administration of disulfiram (200 and 300 mg/kg/day). CONCLUSION: Dithiocarbamates may provide an effective new approach for the treatment of arthritis and other inflammatory diseases.

Animals↗

PubMed1997

Macrophage migration inhibitory factor is involved in the pathogenesis of collagen type II-induced arthritis in mice.

To determine the importance of macrophage migration inhibitory factor (MIF) in the development of arthritis we used an experimental model for rheumatoid arthritis, collagen type II (CII)-induced arthritis in mice. Treatment with neutralizing anti-MIF Abs before immunization of (B10.Q x DBA/1)F1 with CII led to delayed onset and lowered frequency of arthritis. This was associated with lower levels of IgG2a to CII in MIF-depleted mice. The proliferative response to CII was stronger in the anti-MIF-treated mice, whereas no significant effects were seen on Ag-induced IFN-gamma production in response to CII or on the total serum Ab levels in response to CII. These results provide the first experimental evidence of a role for MIF in the pathogenesis of autoimmune disease.

Animals↗

PubMed1996

Interleukin-10 suppresses the development of collagen type II-induced arthritis and ameliorates sustained arthritis in rats.

The collagen-induced arthritis model in DA rats induced with homologous rat type II collagen was chosen to determine the therapeutic capacity and effects on autoimmunity by IL-10. Systemic IL-10 treatment (100 or 10 micrograms/day) with mini-osmotic pumps during the periods of arthritis onset (days 12-20 after immunization) decreased the frequency of arthritis and delayed the onset and reduced the severity of arthritis in the few rats that eventually developed arthritis. Concomitantly, levels of autoantibodies to CII were reduced. To test the activity on established arthritis, IL-10 was administered subcutaneously in the paws. This treatment reduced the swelling but did not block the arthritis process. The effective treatment required 100 micrograms of IL-10 every 12th hour while 50 micrograms of IL-10 had little effect, although a tendency of reduced paw swelling was observed. Surprisingly, therapeutic IL-10 treatment led to higher serum levels of autoantibodies to CII. The highest doses of IL-10 (100 micrograms) did not show any apparent toxic effects when given locally or systematically. Taken together, this study suggests that IL-10 is a candidate for treatment of rheumatoid arthritis.

Animals↗

PubMed1996

Sodium lauryl sulfate effect on the density of epidermal Langerhans cells. Evaluation of different test models.

The effect of different test models for sodium lauryl sulfate (SLS)-induced irritant contact dermatitis on epidermal Langerhans cells (LC) numbers was examined. Finn Chambers, 8 and 12 mm, containing 15 and 34 or 50 microliters, respectively, of 1% aq. solution of SLS were applied to human forearm skin for 48 h as single or repeated application. The results showed a clear difference between the effects with the 2 chamber sizes. The effect of the 8-mm chambers could result in increased, unchanged or decreased LC numbers, while 12-mm chambers always produced a decrease. These results seem to explain, at least partly, the discrepant results reported from various laboratories.

Adult↗

PubMed1994

Distributional changes of Langerhans cells in human skin during irritant contact dermatitis.

We used light and electron microscopic immunocytochemistry to study distributional changes in the human Langerhans cell (LC) system during the first 14 days of a mild irritancy caused by sodium lauryl sulphate (SLS). A marked initial decrease in epidermal LC was noted possibly resulting from migration from the epidermis to the dermis and from irreversible cell damage. Several studies have previously found an unchanged number of LC in SLS-induced contact irritant dermatitis, but these studies may not have taken into account the fact that SLS is effectively absorbed from the test chamber. Unless certain precautions are taken the SLS concentration rapidly falls to topical levels that have no effect on the LC system. Simultaneously with the decrease in the epidermis we observed an increase in dermal CD1a+ cells, confirming an often reported finding. There is, however, no consensus as to the identity of these cells, and several authors have reported that such cells lack LC granules and thus these cells have often been classed as indeterminate cells. We found that, during irritant contact dermatitis, provided an adequate number of sections were scrutinized in the electron microscope, all dermal CD1+ cells contained Birbeck granules.

Adult↗

PubMed1994

Immunocytochemical detection of the carbohydrate antigen, Sialyl Lewis(x), in normal human skin and during irritant contact dermatitis.

Sialys Lewis(x) (SLex) is a ligand for the E-selectin and the interaction of E-selectin on the endothelium and SLex on T cells may be important for T-cell migration into the skin. We investigated the expression of SLex on Langerhans cells (LC) in normal skin and on LC repopulating epidermis deprived of LC due to a preceding irritant contact dermatitis. SLex was visualized by fluorescence and light microscopic immunocytochemistry using the monoclonal antibody, CSLEX-1. The results showed that about 40% of LC in normal epidermis express SLex. In the repopulation phase, most of the epidermal cells were CD1a+/SLex. We suggest that SLex is present on epidermal LC that have recently immigrated from the dermis.

Cell Movement↗

PubMed1993

alpha-Amino-n-butyric acid methyl ester induces concentrative uptake of L-dopa in human Langerhans' cells normally not operative for L-dopa transport.

We recently reported the existence of two kinds of human epidermal Langerhans' cells (LC), one which can take up and accumulate L-dopa and one which cannot. The dopa(+) LC take up L-dopa by carrier-mediated exchange diffusion, that is, the influx of L-dopa and the outflow of an intracellular substance are linked via the same carrier. The nature of the fundamental difference between L-dopa(+) and L-dopa(-) cells has not been clarified. We have now found that alpha-amino-n-butyric acid methyl ester (ABA-OME) penetrates into intracellular compartments, perhaps endosomes or lysosomes, of all LC, where hydrolysis results in the accumulation of the free amino acid (ABA). This accumulation causes a considerable increase in osmotic pressure of the membrane-limited organelle, leading to influx of water and swelling. Co-incubation with L-dopa revealed an influx of L-dopa into LC which normally cannot take up this amino acid. It is suggested that these LC lack the capacity to synthesize and/or store the counterpart which allows L-dopa to enter the dopa(+) LC, but that ABA in the L-dopa(-) LC can function as an equivalent counterpart.

Adult↗

PubMed1992

Reactive changes in human epidermis following simple occlusion with water.

Reactive changes produced in human epidermis by occlusion with water for 24 or 48 h were studied. A focally widened intercellular space was common. Several, often pronounced, reactive events were observed in the Langerhans cell system, whereas the keratinocytes and the melanocytes seemed unaffected. The reactive events showed a scattered distribution and were revealed only by electron microscopic analysis of extensive section series. It seems that, among epidermal cells, the Langerhans cells are the most susceptible and most easily alerted by an exogenous challenge.

Adult↗

PubMed1991

Functionally different Langerhans' cells in human epidermis.

Experiments comparing the L-dopa histofluorescence method for the visualization of epidermal Langerhans' cells and immunocytochemical labelling with monoclonal anti-T6 antibodies have demonstrated the existence of two functionally different human Langerhans' cells: those that take up L-dopa by a mediated transport and those that lack the capacity to take up L-dopa.

Biological Transport↗

PubMed1990

Reactive changes in the Langerhans' cells of human skin caused by occlusion with water and sodium lauryl sulphate.

Human skin was patch tested with sodium lauryl sulphate or with water only for 48 h and biopsied immediately and after 24 h, then analyzed by immunocytochemistry and electron microscopy. Sodium lauryl sulphate produced a decrease in the number of epidermal Langerhans' cells and an increase in dermal Langerhans' cells, with individual variations. The 48-h water occlusion controls showed only slight reactions. Unexpectedly, quite pronounced reactive changes were seen 24 h after termination of water occlusion. Thus, dermal Langerhans' cells were commonly increased and epidermal Langerhans' cells tended to decrease in number. The results indicate that the 24-h interval is not a period of recovery but a period in which more pronounced reactive changes occur. Hydration over 48 h followed by dehydration leading to temporary damage to the epidermal barrier may explain the present findings. Some of the reactive changes observed after sodium lauryl sulphate exposure probably represent the additive effects of occlusion and sodium lauryl sulphate treatment.

Adult↗

PubMed1988

Cytomembrane-sandwiching in human epidermal Langerhans cells: a novel reaction to an irritant.

Relatively mild exposure of human epidermis to sodium lauryl sulphate caused a general activation of the Langerhans cell system within 5 hours. An unexpected reactive phenomenon was that this irritant caused some cytomembrane parts to fold upon each other, thereby forming numerous Birbeck granules, several of which had an irregular shape. Spotty cytomembrane damage to the Langerhans cells was also observed.

Administration, Cutaneous↗