Lymphokine-induced monocyte procoagulant activity is depressed in patients with advanced malignancies.
Fibrin deposition in the microenvironment of tumor cells may be critical to tumor growth and metastasis formation. Procoagulant activities of tumor cells themselves, or of infiltrating macrophages, activated by the host's immune system to the tumor, may both contribute to coagulopathies associated with metastases. Lymphokine (LK) supernatant activated procoagulant activity on normal peripheral blood monocytes but failed to induce activity on mononuclear cells from 18/22 patients with locally advanced or disseminated non-lymphoid tumors. Monocytes from the remaining patients had very low basal levels of MPCA and were less sensitive than normal cells to LK. Monocytes from 4 patients (3 with tumors with a high growth fraction) had extremely elevated levels of basal procoagulant activity, possibly due to maximal activation in vivo. Neither LK nor bacterial lipopolysaccharide (LPS) stimulated procoagulant production of these cells. By contrast, cells from 8/13 patients produced procoagulant in response to LPS. This study indicated that monocyte function of patients with disseminated cancer is suppressed with respect to LK stimulation, but that cells with normal basal levels of MPCA respond to LPS. Preactivation of mononuclear procoagulant in vivo precluded subsequent stimulation by either LPS or LK.
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Geczy
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Ryan
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D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D001779:Blood Coagulation Factors / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008070:Lipopolysaccharides / Q000276:immunology; D008222:Lymphokines / Q000502:physiology*; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology*
D001779:Blood Coagulation Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; C045072:macrophage procoagulant activity