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Natural and antibody-dependent cellular cytotoxicity of polymorphonuclear leukocytes
Abstract:
Cytotoxic activity of polymorphonuclear leukocytes (PMN) in the peripheral blood of patients with various diseases was demonstrated to K562 cells (natural cytotoxicity, NC) and the antibody-coated P815 cells (antibody-dependent cellular cytotoxicity, ADCC), using a 51Cr-release method. The NC values of normal PMN were lower than those of normal lymphocytes with mean values of 5.0% and 30%, respectively. The NC values of patients' PMN were also lower in malignancy, chronic hepatitis and connective tissue diseases. The ADCC values of normal PMN were moderately high with a mean value of 16.0%, which was almost a half of normal lymphocytes. Higher ADCC values of PMN were found in patients with chronic hepatitis, SLE and Behcet's disease, and in these cases the ADCC values of their lymphocytes were extremely low. The supernatants of PMN mix-cultured with unlabeled K562 or the antibody-coated P815 cells were fairly cytotoxic to both cells, though the similar supernatants of lymphocytes were cytotoxic only to K562 cells, but not to the antibody-coated P815 cells.
Insights
Polymorphonuclear leukocytes (PMN) show lower natural cytotoxicity (NC) but higher antibody-dependent cellular cytotoxicity (ADCC) in certain diseases. PMN supernatants exhibit broader cytotoxicity than lymphocyte supernatants.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Polymorphonuclear leukocytes (PMN) are key immune cells.
- Their cytotoxic functions, natural cytotoxicity (NC) and antibody-dependent cellular cytotoxicity (ADCC), are crucial in disease.
- Understanding PMN activity in various diseases is important for immune response studies.
Purpose of the Study:
- To investigate and compare the cytotoxic activities (NC and ADCC) of peripheral blood PMN in patients with different diseases against K562 and P815 cells.
- To evaluate the cytotoxic potential of PMN-derived factors.
Main Methods:
- Utilized the 51Cr-release assay to measure both NC and ADCC.
- Compared PMN cytotoxicity with that of lymphocytes in healthy individuals and patients.
- Analyzed the cytotoxic effects of supernatants from PMN and lymphocyte cultures.
Main Results:
- Normal PMN exhibited lower NC (5.0%) compared to normal lymphocytes (30%).
- Patients with malignancy, chronic hepatitis, and connective tissue diseases showed reduced PMN NC.
- Normal PMN had moderate ADCC (16.0%), about half that of lymphocytes.
- Elevated PMN ADCC was observed in chronic hepatitis, SLE, and Behcet's disease, with concomitant low lymphocyte ADCC.
- PMN supernatants demonstrated cytotoxicity against both K562 and P815 cells, unlike lymphocyte supernatants which were only cytotoxic to K562 cells.
Conclusions:
- PMN cytotoxic activity, particularly ADCC, is altered in specific disease states.
- PMN possess distinct cytotoxic mechanisms and factors compared to lymphocytes.
- These findings highlight the complex role of PMN in the immune response during disease.