In vivo studies of macrophages and intercellular adhesion molecule-1 following lipopolysaccharide treatment in tumour-bearing rats

Abstract

Histological, haematological and immunocytochemical analyses were performed on a mammary adenocarcinoma implanted in Dark Agouti rats treated with LPS to further elucidate the role of TNF-alpha in tumour biology. Tumours were examined 4-12 days after implantation with parallel studies on rats treated with LPS (200 micrograms/100 g bodyweight [b.w.]) 24 h before removal. Tumour tissue from rats with 12-day-old lesions was also examined over the 24 h period after LPS administration. Haemorrhagic necrosis was evident 6 h after endotoxin treatment and became profound by 24 hours, at which stage only a thin band of viable cells was seen at the rim of the tumour. Using immunocytochemical techniques and a monoclonal anti-macrophage antibody, macrophage numbers were seen to increase throughout the tumour following LPS administration at each stage of tumour growth. Immunocytochemical staining for intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule normally involved in monocyte recruitment, could not be detected in vascular channels within the tumours investigated. However, subcutaneous vessels at the tumour periphery produced a strong linear reaction. The results show that macrophage numbers in tumours increase after LPS administration, concurrently with the development of haemorrhagic necrosis. This cellular infiltration was associated with peripheral monocytopenia. ICAM-1 expression on the vascular endothelium within tumours was deficient.