Resident peritoneal macrophages and mast cells are important cellular sites of COX-1 and COX-2 activity during acute peritoneal inflammation

Abstract

Introduction: Cyclooxygenases (COXs) play important roles during inflammation. While reports on COX-2 function in inflammation preceded those on COX-1, it is now well established that both isoforms participate in this process. During inflammation, COX expression was reported in inflammatory leukocytes, but much less is known about their presence in tissue- resident leukocytes. The aim was thus to verify the expression and activity of the COX isoforms in resident peritoneal mast cells and macrophages during acute peritonitis. Materials and Methods: Zymosan peritoneal inflammation was induced in C57BL/6J mice and COX-1 and COX-2 expression was evaluated by RT-PCR (mRNA level) and immunocytochemistry (protein level). COX activity was assessed by a specific assay and prostaglandin production by ELISA. Furthermore, some mice were selectively depleted of either peritoneal mast cells or macrophages and then COX activity was determined. Results: The study revealed that both COXs are expressed/active at the peak of inflammation, but COX-2 predominates during resolution. The expressions of the COXs were detectable in both populations of resident peritoneal leukocytes. In peritoneal macrophages both isoforms were active even during the late phases of peritonitis and the cells significantly contributed to PGE2 and PGD2 synthesis. The most striking observation was that resident macrophages are critical for PGD2 production during the resolution of inflammation. Conclusions: This study documents that both COX isoforms participate in all stages of acute inflammation and that tissue-resident leukocytes, especially macrophages, are important sites of COX-1/COX-2 expression and prostaglandin synthesis. © 2009 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.