Collagen metabolism and phenotype after prostaglandin E2 treatment of granuloma: direct and macrophage-modulated effects

Local administration of PGE₂ (2 μg) to polyether sponges, implanted s.c. in rats, inhibited hydroxyproline and total protein accumulation, without altering relative amounts of collagen, when administered early during granuloma development. In contrast, while DNA as well as total protein accumulation was inhibited by local PGE₂ treatment of established granuloma, hydroxyproline accumulation and the relative amounts of collagen were enhanced. This PGE₂-induced collagen enhancement was associated with an increased type III : type I collagen ratio, possibly due to differential intracellular breakdown of newly synthesized collagen. The solubility of granuloma collagen was unaffected by PGE₂. Impregnation of sponges with carrageenan before implantation, thereby giving macrophage-dominated granuloma, did not affect the changes in protein and DNA induced by later treatment with PGE₂, but did reverse the PGE₂-induced accumulation of hydroxyproline. This latter effect probably reflects macrophage-mediated, PGE₂ enhancement of collagenolytic activity.