Altered tissue-specific opsonic activities and opsono-recognition of liposomes in tumour-bearing rats.
Reticuloendothelial phagocytic and serum opsonic activity was evaluated at terminal stages of tumour growth in rats transplanted subcutaneously with chondrosarcoma in an attempt to evaluate the role of opsonic protein(s) in governing liposome recognition and clearance by the macrophage system. The liver of the tumour-bearing animals manifested a decline in the uptake of multilamellar vesicles composed of egg phosphatidylcholine: cholesterol: dicetyl phosphate (mole ratio 7:2:1) from the 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 liposome recognition in both health and at terminal stages of cancer growth 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 results were comparable to the corresponding liposome-cell interaction in the absence of serum. The opsonic activity of serum derived from tumour-bearing rats could be demonstrated either by prior dialysis of serum against de-ionized water or by addition of EGTA. Liver phagocytes of healthy animals recognized more liposome in the presence of dialysed or EGTA-chelated tumour-serum than that of liver cells derived from tumour transplanted rats. A significant increase in serum calcium concentration was found in all tumour-bearing rats. When the concentration of calcium in the serum of normal animals was increased to the level that is encountered in tumour-bearing rats, a sharp drop in liposome recognition by liver phagocytes was observed. This drop in opsonic activity was not related to changes in the ionic strength of serum. The ammonium sulphate precipitated opsonin was also calcium-sensitive and its opsonic activity was abolished in the presence of calcium. Studies with isolated splenic phagocytes suggested that an increase in the opsonic activity of serum, but not the elevated calcium level, was responsible for hyperphagocytosis of liposomes by the splenic phagocytes of tumour-transplanted animals. The opsonic molecule which enhanced liposome recognition by liver non-parenchymal cells failed to enhance liposome clearance by the splenic phagocytes. These findings suggest that the alteration in macrophage clearance of liposomes during the terminal growth of cancer may be mediated in part by changes in the opsonic capacity of serum.
Moghimi
S M
SM
Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
Patel
H M
HM
D000818:Animals; D002118:Calcium / Q000097:blood*; D008081:Liposomes; D008099:Liver / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D012157:Mononuclear Phagocyte System / Q000502:physiology; D009374:Neoplasms, Experimental / Q000503:physiopathology*; D009895:Opsonin Proteins / Q000502:physiology*; D009994:Osmolar Concentration; D010587:Phagocytosis; D051381:Rats; D013154:Spleen / Q000503:physiopathology
D008081:Liposomes; D009895:Opsonin Proteins; D002118:Calcium