Interferons as modulators of human monocyte-macrophage differentiation. I. Interferon-gamma increases HLA-DR expression and inhibits phagocytosis of zymosan.

Abstract

The development of HLA-DR (Ia) expression in the presence and absence of interferon-gamma was monitored in monocyte-macrophage cultures. Overnight incubation with doses as low as 5 U/ml gave elevated values for Ia expression and the maximum increase was obtained with 200 U/ml. In contrast interferon-alpha had only a slight effect on the expression of Ia at doses as high as 2000 U/ml. The increase seen at 24 hr was maintained during the first 2 days of culture. The interferon-gamma-treated cells expressed four to five times more Ia than fresh monocytes. During the same time, monocytes cultured in the absence of interferon expressed approximately two times the amount of fresh monocytes. When the surface density of Ia was calculated, the interferon-gamma-treated monocytes expressed twice that of the untreated cells. Major changes in morphology and size occurred between days 3 and 4 of monocyte to macrophage development. Consequently a rapid increase in Ia expression took place; however, when the surface density was calculated this value increased only slightly when the monocytes matured to macrophages. The interferon-gamma-treated cells continued to express more total Ia as well as having increased surface density of this antigen. Interferon-gamma was also added to monocyte-macrophages several days after culture initiation (days 3, 4, and 5). Despite being in different stages of maturation, the cells responded to the interferon with increased Ia expression and surface density. The phagocytic activity of opsonized zymosans was also monitored. In contrast to Ia expression, this activity was downregulated by interferon-gamma, and the lower levels of phagocytosis were maintained through the 7 days of observation. Thus, interferon-gamma appears to change the differentiation pathway of the monocyte. The signal stimulates an increased level of Ia that may assist in the initiation of immune responses, and at the same time downregulates the scavenger role of removing opsonized particles. Once the monocyte has received this specific signal it continues to develop in a pathway different from that of the nontreated monocytes.