Human Neutrophils Express the Prostaglandin G/H Synthase 2 Gene When Stimulated with Bacterial Lipopolysaccharide

Abstract

Human blood neutrophils (PMN) rapidly release arachidonic acid (AA) from cellular phospholipids when stimulatedin vitrowith a variety of inflammatory agonists. Free AA is then metabolized via 5′-lipoxygenase to produce bioactive mediators such as leukotriene B₄and 5-hydroxyeicosatetraenoate. Arachidonic acid can also be metabolized via the cyclooxygenase or prostaglandin G/H synthase (PGHS) pathway to form prostaglandins and thromboxane. We show here that human blood PMN express the PGHS 2 gene when stimulated with bacterial lipopolysaccharide (LPS). PGHS 2 mRNA increases within 30 min after LPS stimulation and PGHS 2 immunoreactive protein is detectable by 5 h. Although PGHS 1 mRNA is detectable in PMN, no immunoreactive protein is observed in either resting or LPS-stimulated cells. Following stimulation with LPS and expression of PGHS 2, PMN increase secretion of prostaglandin E₂. This phenotypic change in PMN could be an important mechanism for regulating inflammation.