Role of PLD in Superoxide Formation

Concerning endocytosis, the internalization and degradation of EGF receptors is inhibited by primary, but not secondary alcohols [157]. Overexpression of PLDl and PLD2 reduces surface levels of the EGF receptor, but this is not observed with catalytically inactive mutants [157]. The activation of MAP kinase by EGF depends on the internalization of the EGF receptor [158], and there is evidence that this is inhibited by butan-l-ol, but not butan-2-ol [157]. The fusion of early endosomes may also involve PLD since this is stimulated by exogenous PLD and blocked by butan-l-ol, but not butan-2-ol [159]. A role for the phospholipase in the assembly of clafhrin coats on lysosomes has also been reported [160]. 

Superoxide Ofj production by neutrophils and macrophages is part of the host defenses against microorganisms. PLD has been imphcated in this response because agents that elicit O2 formation also activate PLD [162-164]. In addition, in vitro experiments showed that PA elicited NADPH-dependent O2 formation in neutrophil extracts or intact neutrophils [165, 166]. Some studies also showed a high correlation between O2 production and PA accumulation in neutrophils stimulated with FMLP [167]. Furthermore, treatment of these cells with ethanol decreased both PA formation and O2 generation. 

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