Lymphocyte ATP-ase Activity Research Articles

Changes of enzyme activities recognized in lymphocytes from patients with carcinoma of the gastrointestinal tract

Adenosine triphosphatase (ATPase) activity and acid phosphatase activity in lymphocytes from patients with carcinoma of the gastrointestinal tract were determined in order to investigate whether or not changes in these enzyme activities has any relation to the immune reactivity of carcinoma-bearing patients. In patients with a performance status of more than 60%, the mean value of the total ATPase activity in lymphocytes differed little from that in controls, but the mean value of the oligomycin-sensitive ATPase activity decreased as compared to that in the controls. On the other hand, the mean values of the activities of both free and total acid phosphatase in lymphocytes increased as compared to those in controls. The mean values of the activities of both ATPase and acid phosphatase in lymphocytes from patients whose performance status was less than 50% decreased as compared to those from controls and patients whose performance status was more than 60%. The change of the activities of both ATPase and acid phosphatase in lymphocytes has relation to that of the immunological parameters of the patients with carcinoma of the gastrointestinal tract. These results indicate that both ATPase and acid phosphatase in lymphocytes may play an important role in the immune mechanism.

Changes of adenosinetriphosphatase (ATPase) activities in lymphocytes from patients with carcinomas of the gastrointestinal tract.

The activities of both total and Oligomycin-sensitive ATPase in lymphocytes from patients with gastrointestinal tract (GI) carcinomas in different Karnofsky performance status (KPS) were determined to investigate whether or not the changes of these enzyme activities were correlated to those of the immune responsiveness of the patients. In the patients whose KPS indicated more than 50%, the mean value of the total ATPase activity in lymphocytes tended to increase slightly as compared with that determined in the control subjects, but the mean value of the Oligomycin-sensitive ATPase activity in lymphocytes tended to decrease slightly as compared with that determined in the control subjects. In the patients whose KPS indicated less than 30%, the mean values of the activities of both total and Oligomycin-sensitive ATPase in lymphocytes tended to decrease remarkably as compared with those determined in the control subjects. The ATPase activities in lymphocytes were suggested to be useful measures to the immune responsiveness of the patients with GI carcinomas.

Lymphocyte ATPase activity in patients with carcinoma of the larynx. A follow-up study on 45 patients.

Mitochondria-related Mg ATPase activity was assayed in lymphocytes isolated from the blood in 45 patients with epidermoid carcinomas of the larynx. Increased activity was found in 11 patients and normal or subnormal activity in the remaining cases. No correlation could be demonstrated between the magnitude or the spreading of the malignancy as recorded by the TNM classification and the ATPase activity. In 36 patients determinations were carried out repeatedly during a period from 6 to 20 months following therapy and after 3 years a final follow-up on all patients was done. All patients received high-voltage radiotherapy and in 7 patients additional partial or total laryngectomia was carried out, one patient had bilateral neck dissection. After radiotherapy the ATPase activity decreased significantly in 17 patients while it either remained normal or increased temporarily in the rest. No correlation was found between the course of the disease and the initial ATPase activity or the pattern of variation in ATPase activity following therapy. Contrary to what resulted from a preliminary study, it is concluded that determination of lymphocyte ATPase activity is of no diagnostic value in patients with laryngeal carcinoma, nor does it offer any prognostic help in determining which patients may relapse or develop metastatic disease.

Cell‐mediated immunity in juvenile periodontitis and levamisole treatment

Immunostimulation with levamisole was attempted in eight patients with juvenile periodontitis and six reference patients with gingivitis but without loss of periodontal attachment. The following parameters were studied before and after levamisole treatment: gingival status, the concentration of serum immunoglobulins and complement, T and B lymphocyte ratio, leukocyte migration inhibition and lymphocyte transformation responses by dental plaque bacteria, PPD or PHA, and lymphocyte ATP-ase activity. In juvenile periodontitis cell-mediated immunity to dental plaque antigens seemed to be impaired, but the response was not restored by treatment with levamisole. There was no evidence of a broader suppression of cell-mediated immunity in juvenile periodontitis and there was no significant clinical effect of levamisole treatment. It is suggested that the apparent suppression of in vitro cell-mediated immunity to dental plaque bacteria in juvenile periodontitis is a secondary change, caused by a long-standing chronic infection.

ATP-ase activity of purified human normal T- and B-lymphocytes.

In 15 healthy individuals the ATP-ase activity of circulating B-lymphocytes was found to be significantly higher than of T-lymphocytes. Two different methods were used for the purification of B- and T-lymphocytes and the result was independent of which one of these methods was used. The demonstration of different ATP-ase activities of unstimulated B- and T-lymphocytes corresponds well with previously published histochemical findings in lymphatic tissues examined for ATP-ase activity. It is concluded from the present study that because of overlapping values determination of the lymphocyte ATP-ase activity cannot serve as a single marker for the B- and T-cell nature of human lymphocytes, but demonstration of an unusual high ATP-ase activity in unstimulated lymphocytes will serve as additional identification of these as belonging to the B-lymphocyte population.

Increased ATP-ase activity of lymphocytes after rosette formation with sheep red blood cells.

In a number of experiments it was demonstrated that in the E-rosette assay for human T-lymphocytes using sheep red blood cells, the ATP-ase activity of the lymphocytes increased in proportion to the number of rosettes being formed. Also, after increasing the number of rosettes by treatment of the sheep red blood cells (SRBC) with neuraminidase and after diminishing the number of rosettes by treatment of the lymphocytes with antilymphocyte globulin (ALG), change in the ATP-ase activity was proportional to alterations in the number of rosettes being formed. ALG itself stimulated the lymphocyte ATP-ase activity, possibly through activation of the same receptor sites as used by SRBC.

Lymphocyte ATP-ase activity in treated cases of Hodgkin's disease.

The ATP-ase activity was determined in lymphocytes isolated from peripheral blood in 41 patients with Hodgkin's disease and 50 healthy controls. All patients were previously treated with irradiation or cytostatic drugs and 17 patients were under maintenance therapy at the time of investigation. A significantly increased ATP-ase activity was found in lymphocytes from patients with Hodgkin's disease. The individual activities were unrelated to the clinical stage of the disease, but correlated to the histological classification of the lymphatic tissue. Significantly lower lymphocyte ATP-ase activity was found in patients under maintenance treatment with immunosuppressive drugs, especially if the patients had previously been irradiated. It is suggested that the ATP-ase activity of circulating lymphocytes is related to the immunological activity against the presence of the malignant cells in Hodgkin's disease.

Elevated lymphocyte ATP-ase activity in patients with cancer of the uterine cervix.

Elevated lymphocyte Adenosine Tri-Phosphatase (ATP-ase) activity was found in 23 och 28 patients with cervical uterine carcinomas of various stages. Treatment with external irradiation and radium insertion was followed by a decline in the lymphocyte ATP-ase activity in 22 patients, while the activity remained unchanged in one patient. No correlation between the tumour stage and the lymphocyte ATP-ase activity was demonstrated. In 24 patients the clinical effect of the treatment was well correlated with the decline in ATP-ase activity. It is suggested that the determination of lymphocyte ATP-ase activity could be valuable in screening for cervical carcinoma and for follow-up after radical treatment.

ATP-ase activity of lymphocytes from patients with carcinomas of the urinary bladder.

In 13 out of 26 patients with urinary bladder carcinomas in various stages of malignancy, the ATP-ase activity of circulating lymphocytes was found significantly elevated. A decline in the ATP-ase activity was demonstrated in 14 of 17 patients re-investigated after treatment, while the activity remained unchanged in 2 and rose in 1 patient. No correlation between the clinical tumour stage and the lymphocyte ATP-ase activity was found, but the activity was closely correlated to the histological grade of malignancy. In 11 of the 17 patients the clinical effect of the treatment was closely correlated to a decline in ATP-ase activity. Determination of lymphocyte ATP-ase activity is suggested as an additional and simple help in the diagnosis of bladder carcinoma and in the follow-up control after treatment of patients with this disease.

Ouabain-sensitive and oligomycin-sensitive adenosine-triphosphatase activities of normal human lymphocytes.

Summary. Homogenates of highly purified normal human lymphocytes contained two different adenosinetriphosphatase (ATPase) activities. One of these activities was present in a supernatant fraction of the lymphocyte homogenates, possibly related to mitochondria. This activity was independent of the presence of monovalent cations, was insensitive to ouabain, but was inhibited by oligomycin and stimulated by 2,4 dinitrophenol. Exchange of Mg++ with Ca++, or addition of sodium fluoride completely inhibited this ATPase activity. A Km‐value for the substrate ATP was determined to be 0.83 mm. The specific activity of the oligomycin‐sensitive, supernatant ATPase was 0.31 ± 0.13 (SD) μmoles Pi per mg protein per 30 min.The other ATPase activity was activated by Na+ and K+ and was inhibited by ouabain. This ATPase activity was only found in the pellet fraction after centrifugation, possibly associated with the cell membranes. The specific activity of this ATPase was 0.25 ± 0.09 (SD) μmoles Pi per mg protein per 30 min. The effect of ouabain in various cation combinations of the assay is reported. Optimal ouabain‐sensitive ATPase activity was found at 100 mm Na+, 15 mm K+ and 6 mm Mg++.Only the oligomycin‐sensitive ATPase activity increased after short time stimulation of the lymphocytes by phytohaemagglutinin (PHA), and this could be inhibited by puromycin.The increased ATPase activity of normal lymphocytes caused by the non‐specific mitogen PHA suggest the possibility that the increased ATPase activity of lymphocytes from patients with malignant tumours could be due to a stimulation of the lymphocytes by tumour specific antigens in vivo.

ATP-ase activity of lymphocytes from normal individuals and patients with cancer.

The lymphocyte ATP-ase activity was significantly elevated in three groups of cancer patients compared to the activity of lymphocytes from normal individuals and patients with various nonmalignant diseases. Oligomycin inhibited and 2, 4 dinitrophenol stimulated the ATP-ase activity of the lymphocytes from both groups, indicating a contribution of the mitochondrial ATP-ase. Incubation of normal lymphocytes with phytohemagglutinin in vitro increased the oligomycin-sensitive ATP-ase activity of the cells considerably. It is suggested that the significantly elevated ATP-ase activity of lymphocytes from cancer patients is probably due to an in vivo stimulation following a reaction between lymphocytes and tumor antigens.