Search

Kupffer cells (liver macrophages) possess the ability to secrete a wide array of biologically active compounds including reactive oxygen species, nitric oxide (NO), eicosanoids and cytokines1–4. The synthesis and release of these mediators has been shown to be elicited by a number of agents including phagocytotic material (zymosan, viruses, bacteria), tumor promoting agents (phorbol ester) and other biologically active substances1–5.

The liberation of arachidonic acid (AA) is thought to be the rate-limiting step in prostanoid synthesis of rat-liver macrophages (RLM)1. The best known pathway for AA-liberation is elicited by the activation of a phospholipase (PL)A2 hydrolysing the ester-bond in sn-2-position of phospholipids2. It has been shown that RLM express a cPLA2 very similar to cPLA2 recently identified in U937 cells2: the enzyme has an apparant molecular weight of 100 kDa in SDS-polyacrylamide-gelelectrophoresis (PAGE), an alkaline pH-optimum, is strictly dependent on the presence of Ca2+ in the range from 10−7–10−6 M and shows a Ca2+-dependent translocation to cellular membranes1,2. cPLA2 phosphorylation by mitogen activated protein (MAP) kinase is also discussed as a mechanism for cPLA2 activation3. Another pathway leading to AA-release in RLM involves the activation of a PLC leading to free diacylglycerol (DAG), which serves as substrate for DAG-lipase to liberate free AA4.

Liver macrophages possess the ability to secrete a wide array of biologically active compounds including cytokines, nitric oxide, oxygen radicals and eicosanoids. Eicosanoid formation has been shown to be elicited by a number of particulate (bacteria, viruses, zymosan, immune complexes) and soluble (phorbol ester, PAF, C3a, fluoride, calcium ionophore, LPS, cytokines) agents. The release of arachidonic acid (AA) and eicosanoids in these cells has been shown to be controlled by glucocorticoids (1), intracellular pH (2), calcium ions (3,4), protein kinase (PK) C (5–7) and albumin in the cell media (8).

Liver macrophages possess the ability to secrete a wide array of biologically active compounds including reactive oxygen species, nitric oxide (NO), eicosanoids and cytokines1–4. The synthesis and release of these mediators has been shown to be elicited by a number of agents including phagocytotic material (zymosan, viruses, bacteria), tumor promoting agents (phorbol ester) and other biologically active substances1–5.

Rat liver macrophages (RLM), activated by a variety of agents, are known to release various eicosanoids including prostaglandin (PG)E2 and PGD2 1. The formation of prostanoids is strictly dependent on Ca2+ and is thought to be determined by the activation of a phospholipase (PL)A2 2 and the expression of prostaglandin H synthase (PGHS)-2. It has been shown that RLM express an intracellular cPLA2 which is strictly Ca2+-dependent in the range from 10-7-10-6 M and which shows a Ca2+-dependent translocation to cellular membranes3,4. cPLA2 phosphorylation has been shown to be most likely catalysed by mitogen activated protein (MAP) kinase4. Further evidence has been provided that in addition to regulation by cPLA2, release of prostanoids in RLM is also dependent on the expression of PGHS-25.