The migration of neutrophils (PMN) and monocytes in response to chemotactic factors (CF) and the subsequent production of toxic oxygen intermediates are critical to host defense against bacteria and tumors. CF stimulate the oxidative burst and enhance the production of O?2? by PMN upon subsequent stimulation with phorbol myristate acetate or opsonized zymosan. We have found this enhanced activity is due to a quantitative increase in the membrane oxidase. Stimulation of PMN with CF (C5a, f-Met-Leu-Phe) also triggers a bimodal chemiluminescence response. We have found that this bimodal response represents a primary response at 1 to 2 min due to O?2? generation and a secondary response at 5 to 10 min dependent upon myeloperoxidase release. In an effort to analyze simultaneously chemotactic-receptor binding and cell function, we have produced fluorescent C5a, f-met-leu-phe, and casein derivatives that retain their biologic activity. These factors bind to greater than 90% of PMN, greater than 70% of monocytes, and less than 10% of lymphocytes, and binding is specific for each factor. Data indicate that these receptors are independent and simultaneously present on PMN and monocytes. These probes are being utilized with flow cytometry assays for NADPH, H?2?O?2? production, and phagocytosis to analyze the mechanism of activation of the respiratory burst. The mechanism for attracting lymphocytes to a site in vivo is unknown. We have defined a human T-lymphocyte CF made by T cells in response to mitogen or antigen. CF is attributable to two peptides of approximately 14,000 and 53,000 M.W., produced by human suppressor/cytotoxic T cells, and specifically attract helper/inducer T cells. Studies indicate that in vitro migration of T lymphocytes in response to casein or T-lymphocyte CF is suppressed in patients with established malignancy but not with benign tumors. These patients are also impaired in their ability to produce lymphocyte CF. Evidence suggests that inhibited migration and chemotactic factor production are due to a direct action of a suppressor cell population. Suppressed T-cell migration in patients with malignancy may partially explain their decreased cellular immunity. (LB)
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