Additional evidence for the role of hyaluronic acid in the macrophage disappearance reaction.

A slight macrophage disappearance reaction was elicited in C3H/Hej mice, a low responder strain. Low levels of hyaluronic acid accumulated in the peritoneal fluid during the disappearance reaction, in keeping with the low response. The macrophage disappearance reaction was not simulated by the intraperitoneal injection of large amounts of hyaluronate into nonsensitized C3H/Hej mice. This suggested that these macrophages were refractory to hyaluronic acid. Subsequent experiments demonstrated that low concentrations of hyaluronic acid did not agglutinate these cells, in vitro, nor inhibit their migration to the extent obtained with macrophages from the responder mice (C57BL/6 strain), thus providing evidence that the low responder mice had at least two defects with respect to the disappearance reaction: 1) they accumulated less hyaluronic acid in their peritoneal fluid, and 2) their macrophages were refractory towards hyaluronic acid. Generalized defects in membranes of various cell types of C3H/Hej mice, involving receptors for lymphokines in the case of mesothelial cells, or hyaluronic acid receptors on macrophages may serve as the central defect and explain the above observations.