Received for publication November 20, 2007.
Revised January 28, 2008.
Accepted for publication January 31, 2008.

Prostaglandin I₂ Plays a Key Role in Zymosan-Induced Mouse Pleurisy

Abstract

Zymosan, the cell wall of Saccharomyces cerevisiae, induces innate immune responses involving prostanoid production and complement activation. However, the roles of prostanoids in zymosan-induced inflammation and their interaction with the complement system remain to be determined. To clarify these issues, we examined zymosan-induced pleurisy in mice lacking receptors for prostaglandin (PG) E₂ (EP^-/- mice) or PGI₂ (IP^-/- mice). Zymosan-induced exudate formation was significantly reduced in IP^-/- mice compared with wild-type (WT) mice, while none of EP^-/- mice (EP₁^-/-, EP₂^-/-, EP₃^-/- and EP₄^-/- mice) showed any significant difference from WT mice. Furthermore, indomethacin, an inhibitor of prostanoid biosynthesis, suppressed exudate formation in WT mice to almost the same level as that of IP^-/- mice. Accordingly, significant production of PGI₂ in the pleural cavity, suggested to be cyclooxygenase-2 dependent, was observed after zymosan injection. Complement activation in the pleural cavity after zymosan injection was confirmed, and pre-injection of cobra venom factor (CVF), to deplete blood complement C3, significantly suppressed following zymosan-induced exudate formation in WT mice. Simultaneous treatment with indomethacin and CVF further suppressed exudate formation in WT mice compared to each treatment alone. Since, some degree of exudate formation was still observed, other factor(s) seem to be involved. However, platelet activating factor, a promising candidate as one such a factor, was not involved in zymosan-induced exudate formation. These results clearly indicate that the PGI₂-IP system together with the complement system plays a key role in exudate formation in zymosan-induced pleurisy.

Key words: complement, inflammation, innate immunity, knockout mice, prostacyclin, zymosan