Phospholipases in the Macrophage
It is well established that the synthesis of prostaglandins and leukotrienes is dependent on the availability of free arachidonic acid, which is normally found esterified in the sn-2position of phospholipids. The controlling step of this production has been suggested to be at the level of arachidonic acid release from membrane phospholipids. A likely mechanism for this control is the activation of a phospholipase, probably one localized in the membranes of cells. The phospholipases comprise a widespread and abundant class of enzymes in biological systems (Dennis, 1983). They are defined by their positional specificity on the phospholipid backbone, as shown in Fig. 1. Many phospholipases have been suggested as possible modulators of arachidonic acid release. Figure 2 summarizes the various possible routes by which arachidonic acid can be released. The numerous enzyme sequences that lead to arachidonic acid release begin with one of three enzymes: phospholipase A 1 phospholipase A2, or phospholipase C. The phospholipase A2 route would be the simplest and most direct source of arachidonic acid. The second route would begin with a phospholipase A1 followed by a lysophospholipase. The last begins with a phospholipase C followed by any number of other enzymes. A number of these enzymatic systems have been detected in a variety of circulating cell types including the platelet, polymorphonuclear leukocyte, and macrophage (Bell et al., 1979; Billah et al., 1981; Kroner et al., 1982; Lanni and Franson, 1981; Wightman et al., 1981a,b, 1982).
KeywordsArachidonic Acid Arachidonic Acid Release Crude Homogenate Free Arachidonic Acid Arachidonic Acid Production
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