Importance of local proliferation in the expanding Kupffer cell population of rat liver after zymosan stimulation and partial hepatectomy

Abstract

Partial hepatectomy and a single intravenous injection of zymosan were used to provoke expansion of the Kupffer cell population in rat liver. The number of Kupffer cells per microscopic field increased exponentially for 4 to 5 days after either stimulation. During this exponential growth phase, high mitotic activity of Kupffer cells was observed. The rate of mitosis, based on counts of cells arrested in metaphase by vinblastin, was compared with the increase in total cell population. During the first 3 days after partial hepatectomy, local proliferation was sufficient to explain the increase in population since the mean potential doubling time was 1.3 days compared to an observed doubling time of 3.7 days. During the first 3 days after zymosan stimulation, observed doubling time was 4.3 days compared with the mean potential doubling time of 5.2 days which led to the conclusion that growth is largely due to local proliferation of Kupffer cells. In both experimental situations, extrahepatic recruitment of "resident-type" macrophages was required during the last 2 days of the growth phase, since mitotic activity became too low to explain the observed growth. Proliferating Kupffer cells had characteristics of mature resident macrophages and were, therefore, considered to be different from elicited "exudate-type" cells, such as monocytes.