Mouse tumor-associated macrophages do not generate procoagulant activity in response to different stimuli.
Mononuclear phagocytes, an integral part of the lymphoreticular infiltrate of human and experimental tumors, might contribute to fibrin deposition within malignant tissues through the production of procoagulant activity (PCA). We have studied the PCA of tumor-associated macrophages (TAM) in 2 poorly immunogenic, metastatic murine sarcomas (mFS6 and MN/MCA1); peritoneal macrophages (PM) from tumor-bearing and control animals were also studied, as reference cell populations. PCA was evaluated by a one-stage clotting assay immediately after isolation (basal PCA) and following in vitro stimulation. Basal PCA was very low (less than 1 U/10(4) macrophages) in all cell preparations. Exposure of PM from both normal and tumor-bearing animals to bacterial endotoxin (lipopolysaccharide, LPS), phorbol myristate acetate (PMA) or the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP) resulted in 10-, 7- and 3-fold increases in PCA, respectively. In contrast, TAM from mFS6 and MN/MCA1 consistently failed to generate PCA in response to different concentrations of the same stimuli. Treatment of TAM with aspirin did not affect cell unresponsiveness. Fluorescence microscopy showed that almost all PM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 10% of the TAM were stained. These data, coupled with previous evidence that TAM have a lower number of specific binding sites for phorbol esters than PM, suggest that the defective responsiveness of TAM to endotoxin, PMA and, possibly, FMLP, is due to the lack, or very low expression, of binding sites for these agents on the cell surface. The tumor environment may orient the functional status of in situ macrophages in a direction less favorable to the host.
Erroi
A
A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Casali
B
B
Donati
M B
MB
Mantovani
A
A
Semeraro
N
N
D000818:Animals; D001779:Blood Coagulation Factors / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012016:Reference Values; D012513:Sarcoma, Experimental / Q000473:pathology / Q000503:physiopathology*
D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity