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Procoagulant activity of human alveolar macrophages: different expression in patients with lung cancer
Abstract:
Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of many malignant tissues, might contribute to tumor-associated fibrin deposition through the production of procoagulant activity (PCA). We have studied the PCA of human alveolar macrophages in 28 patients with primary lung cancer and in 9 control subjects. Alveolar macrophages (greater than 97% esterase positive) were isolated form bronchoalveolar lavage fluids by adherence onto plastic. PCA was evaluated by a one-stage clotting assay immediately after isolation (basal PCA) and after incubation (4 hr at 37 degrees C) in the absence and in the presence of endotoxin. Cells from control subjects had low basal PCA (3.9 +/- 1.0 units/5 X 10(4) cells) but, upon exposure to endotoxin, they displayed a 5- to 16-fold increase in PCA. In patients, different patterns of PCA were observed. In the 8 patients in whom lavage had been carried out on the contralateral side to the neoplasm, alveolar macrophages behaved essentially like those from controls. In contrast, in the 20 patients in whom macrophage populations close to the site of the tumor were examined, PCA was abnormal in many respects. In 12 of these, alveolar macrophages had basal PCA comparable to or somewhat lower than control cells, but exhibited a poor procoagulant response when incubated in vitro in the presence of endotoxin. Alveolar macrophages from the remaining 8 patients expressed far higher levels of basal PCA than control cells (25.1 +/- 5.9 units as compared to 3.9 +/- 1.0 units/5 X 10(4) cells). These cells retained their ability to respond to endotoxin in vitro with a 3-fold increase in PCA. In all instances, alveolar macrophage PCA had the characteristics of tissue factor. These data suggest that the presence of primary lung cancer may modulate the expression of PCA in alveolar macrophages close to the tumor site. PCA might be useful to better characterize the functional state of macrophages near the tumor.
Insights
Mononuclear phagocytes near lung tumors show altered procoagulant activity (PCA). This altered PCA in alveolar macrophages may indicate a modified functional state in cancer patients, potentially aiding tumor characterization.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- Mononuclear phagocytes are present in malignant tissues and may influence fibrin deposition.
- Procoagulant activity (PCA) in macrophages could play a role in tumor-associated coagulation.
Purpose of the Study:
- To investigate the procoagulant activity (PCA) of human alveolar macrophages in patients with primary lung cancer.
- To compare PCA levels in macrophages from tumor-adjacent sites versus contralateral sites and control subjects.
Main Methods:
- Alveolar macrophages were isolated from bronchoalveolar lavage fluids of lung cancer patients and controls.
- Basal PCA was measured, along with response to endotoxin stimulation in vitro.
- PCA was characterized using a one-stage clotting assay and assessed for tissue factor activity.
Main Results:
- Alveolar macrophages from control subjects showed low basal PCA but increased significantly with endotoxin.
- Macrophages from lung cancer patients near the tumor exhibited varied PCA: some had low response to endotoxin, while others showed significantly higher basal PCA.
- Macrophages from sites contralateral to the tumor behaved similarly to controls.
Conclusions:
- Primary lung cancer modulates procoagulant activity (PCA) in alveolar macrophages proximal to the tumor.
- Altered PCA in tumor-associated macrophages may serve as a biomarker for their functional state and potentially aid in cancer characterization.