Role of arachidonic acid in neutrophil function

LTA4 generated is almost all converted into LTB4. Thus, LTB4 is the major lipoxygenase product of fMet-Leu-Phe-stimulated neutrophils. 

Neutrophil preparations stimulated with A23187 also generate products of 15 -lipoxygenase activity, such as LTC4. However, most neutrophil preparations also contain eosinophils (usually about 2-5% contamination of the neutrophils). In contrast to neutrophils, which generate large quantities of 

Other roles of arachidonic acid include activation of the NADPH oxidase in the cell-free system (see 5.3.2.3). It may be required for membrane fusion during the process of recruitment of oxidase and receptor molecules from the membranes of specific granules. Finally, there is some evidence that arachidonic acid may  

These latter observations suggest a role for arachidonic acid as a genuine second messenger, and further work is necessary to assess if such a role exists during neutrophil activation. It has also been proposed that arachidonic acid may dissociate p21rac and GDI ( 5.3.2.3), thus allowing the small GTP-binding protein to interact with pAl-phox and p66-phox in the assembly of active NADPH oxidase complexes. 

The role of protein kinase C in many neutrophil functions is undisputed and has been recognised for some time. For many years it was believed that the source of DAG, the activator of protein kinase C, was derived from the activity of PLC on membrane phosphatidylinositol lipids. Whilst this enzyme undoubtedly does generate some DAG (which may then activate protein kinase C), there are many reasons to indicate that this enzyme activity is insufficient to account for all the DAG generated by activated neutrophils. More recently, experimental evidence has been provided to show that a third phospholipase (PLD) is involved in neutrophil activation, and that this enzyme is probably responsible for the majority of DAG that is formed during cell stimulation. The most important substrate for PLD is phosphatidylcholine, the major phospholipid found in neutrophil plasma membranes, which accounts for over 40% of the phospholipid pool. The sn-1 position of phosphatidylcholine is either acyl linked or alkyl linked, whereas the sn-2 position is invariably acyl linked. In neutrophils, alkyl-phosphatidylcholine (1-0-alky 1-PC) represents about 40% of the phosphatidylcholine pool (and is also the substrate utilised for PAF formation), whereas the remainder is diacyl-phosphatidylcholine. Both of these types of phosphatidylcholine are substrates for PLD and PLA2. 

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