Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin.

BACKGROUND: Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells. METHODS: MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD). RESULTS: MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends. CONCLUSIONS: MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.

The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels.

CONTEXT: Lead toxicity is an ongoing concern worldwide, and children, the most vulnerable to the long-lasting effects of lead exposure, are in urgent need of a safe and effective heavy metal chelating agent to overcome the heavy metals and lead exposure challenges they face day to day. OBJECTIVE: This clinical study was performed to determine if the oral administration of modified citrus pectin (MCP) is effective at lowering lead toxicity in the blood of children between the ages of 5 and 12 years. METHOD: Hospitalized children with a blood serum level greater than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry (GFAAS), who had not received any form of chelating and/or detoxification medication for 3 months prior were given 15 g of MCP (PectaSol) in 3 divided dosages a day. Blood serum and 24-hour urine excretion collection GFAAS analysis were performed on day 0, day 14, day 21, and day 28. RESULT: This study showed a dramatic decrease in blood serum levels of lead (P = .0016; 161% average change) and a dramatic increase in 24-hour urine collection (P = .0007; 132% average change). CONCLUSION: The need for a gentle, safe heavy metal-chelating agent, especially for children with high environmental chronic exposure, is great. The dramatic results and no observed adverse effects in this pilot study along with previous reports of the safe and effective use of MCP in adults indicate that MCP could be such an agent. Further studies to confirm its benefits are justified.

Inhaled recombinant alpha 1-antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse.

In alpha 1-antitrypsin deficiency in humans, inadequately regulated activity of serine protease activity is responsible for the chronic lung tissue degeneration and irreversible loss of pulmonary function seen in those individuals with emphysema. Typically, disease symptoms in this patient population are exacerbated by cigarette smoke. Here we show that inhaled recombinant alpha 1-antitrypsin (rAAT) can provide significant protection against the development of emphysema in cigarette smoke-treated mice. As has been reported previously, cigarette smoke was seen to increase significantly the recruitment of neutrophils and macrophages into the lungs of these animals, leading to concomitant alveolar airspace enlargement and emphysema. In smoking animals treated for 6 months with inhaled rAAT, effects on lavage levels of neutrophils and macrophages were only moderate when compared with untreated animals. Furthermore, neutralizing antibodies to rAAT were generated in all rAAT-treated animals. Despite this, however, reductions in airspace enlargement of up to 73% were observed. These findings demonstrate that delivery of rAAT directly to the lungs of smoke-treated mice can inhibit lung tissue damage mediated by proteases, suggesting that rAAT inhalation therapy might represent a practical approach towards treating emphysema in humans, by modifying the course of the disease.