Macrophage Populations in Different Stages of Induced Hepatic Metastases in Rats: an Immunohistochemical Analysis

Abstract

Macrophages play a role in the host defence against cancer. Little is known about changes in macrophage populations during early metastatic growth. To evaluate the distribution, number and phenotype of macrophages in the development of hepatic metastases in a rat model (Wag/Rij rats and syngeneic CC531 colon carcinoma cell line), an immunohistochemical study was performed with the monoclonal antibodies ED1 (monocytes, and all macrophages), ED2 (resident tissue macrophages, like Kupffer cells) and ED3 (a subpopulation of macrophages which may play a role in the recruitment of lymphocytes). OX19 and His14 were used to identify lymphocytes. In this study a new monoclonal antibody CC52 is described, which recognizes the CC531 tumour cell line. Liver metastases were induced by injection of CC531 colon carcinoma cells into a mesenteric vein. Rats were killed at various intervals. Results show three major macrophage populations during hepatic tumour growth: (1) on day 3, infiltrates are observed around the micrometastases, which contain mainly newly recruited macrophages (ED1+ and ED2-); (2) after 7 days, ED3-positive (ED3+) macrophages together with T lymphocytes are found in the infiltrates; (3) an increase in the number of ED2-positive (ED2+) Kupffer cells is observed in the liver parenchyma after 14 days. In conclusion, the present results suggest that various populations of macrophages, newly recruited (ED1+) as well as resident Kupffer cells (ED2+), are involved in the immune response against tumour cell deposits in the liver.

Unique activation of matrix metalloproteinase-9 within human liver metastasis from colorectal cancer

“…this may be due to differences among various macrophage subpopulations (Heuff et al, 1993). It is reported that tumour-associated macrophages (TAMs) may be involved in the development of liver metastasis (Martin et al 1989: Heuff et al 1993. Heuff et al (1993) observed tumourinfiltrating macrophages.…”

“…It is reported that tumour-associated macrophages (TAMs) may be involved in the development of liver metastasis (Martin et al 1989: Heuff et al 1993. Heuff et al (1993) observed tumourinfiltrating macrophages. a peculiar type of TAM.…”

Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis

“…12 However, most studies describing the in situ KC-tumor cell interactions focused on events occurring 2-3 weeks after tumor cell inoculation, 20,22,34,35 and only a few studies examined the early stages of hepatic metastases (Ͻ 24 hr). 36,37 Routine microscopic methods are not optimal for studying early hepatic metastasis because they require thin sections, low sampling volumes, complicated preparation methods and immunohistochemical procedures. 38 In contrast, confocal laser scanning microscopy (CLSM) enables the study of large sample volumes and sections 50 -100 m thick, facilitating investigation of rare cellular events such as the occurrence of tumor cells in the liver.…”

Intradermal Injection of Monocyte Chemoattractant Protein-1 Induces Emigration and Differentiation of Blood Monocytes in Rat Skin

“…These antibodies include ED1, ED2, ED3, Ki-M2R, and TRPM-3 [13, 14, 15, 16, 17, 18]. According to the results from previous immunohistochemical studies on an antigen-induced arthritis in rats [19, 20], ED1-positive monocytes (or newly recruited macrophages) and ED3-positive exudate-type macrophages infiltrated in the early phase of the arthritis, whereas ED2-positive resident (tissue-associated) macrophages were found in the late phase.…”