ALTERED TISSUE-SPECIFIC OPSONIC ACTIVITIES AND OPSONO-RECOGNITION OF LIPOSOMES IN TUMOR-BEARING RATS

Reticuloendothelial phagocytic and serum opsonic activity was evaluate d at terminal stages of tumour growth in rats transplanted subcutaneou sly with chondrosarcoma in an attempt to evaluate the role of opsonic protein(s) in governing liposome recognition and clearance by the macr ophage system. The liver of the tumour-bearing animals manifested a de cline in the uptake of multilamellar vesicles composed of egg phosphat idylcholine: cholesterol: dicetyl phosphate (mole ratio 7:2:1) from th e blood when compared to healthy animals. In contrast, an increase in splenic clearance of liposomes was encountered in tumour-bearing rats. Studies with isolated liver non-parenchymal cells suggested that lipo some recognition in both health and at terminal stages of cancer growt h is influenced by a serum opsonin, which can be precipitated by 35-50 % ammonium sulphate, as well as the concentration of calcium levels in serum. Serum of healthy animals equally enhanced liposome recognition by the hepatic macrophages of both normal and tumour-bearing rats. In contrast, both cell populations manifested poor liposome recognition in the presence of serum pooled from tumour-bearing animals and the re sults were comparable to the corresponding liposome-cell interaction i n the absence of serum. The opsonic activity of serum derived from tum our-bearing rats could be demonstrated either by prior dialysis of ser um against de-ionized water or by addition of EGTA. Liver phagocytes o f healthy animals recognized more liposome in the presence of dialysed or EGTA-chelated tumour-serum than that of liver cells derived from t umour transplanted rats. A significant increase in serum calcium conce ntration was found in all tumour-bearing rats. When the concentration of calcium in the serum of normal animals was increased to the level t hat is encountered in tumour-bearing rats, a sharp drop in liposome re cognition by liver phagocytes was observed. This drop in opsonic activ ity was not related to changes in the ionic strength of serum. The amm onium sulphate precipitated opsonin was also calcium-sensitive and its opsonic activity was abolished in the presence of calcium. Studies wi th isolated splenic phagocytes suggested that an increase in the opson ic activity of serum, but not the elevated calcium level, was responsi ble for hyperphagocytosis of liposomes by the splenic phagocytes of tu mour-transplanted animals. The opsonic molecule which enhanced liposom e recognition by liver non-parenchymal cells failed to enhance liposom e clearance by the splenic phagocytes. These findings suggest that the alteration in macrophage clearance of liposomes during the terminal g rowth of cancer may be mediated in part by changes in the opsonic capa city of serum.