Receptor-mediated phagocytosis in human neutrophils is associated with increased formation of inositol phosphates and diacylglycerol. Elevation in cytosolic free calcium and formation of inositol phosphates can be dissociated from accumulation of diacylglycerol.

Abstract

Phagocytosis of C3bi-or IgG-opsonized yeast particles in human neutrophils was found to be associated with an increased formation of inositol phosphates and diacylglycerol. Pertussis toxin only marginally affected phagocytosis of IgGand C3bi-opsonized particles and the associated formation of second messengers. Forskolin, which induced a threefold rise of cellular cAMP, however, markedly inhibited both C3bi-and IgG-mediated phagocytosis as well as the particle-induced formation of inositol phosphates and diacylglycerol. These observations are in contrast to what was found to occur with chemotactic factors and indicate that chemotactic and phagocytic signaling can be regulated independently in human neutrophils.Since C3bi-mediated phagocytosis has been shown to occur at vanishingly low cytosolic free calcium levels, calcium-depleted cells were used to study the importance of the inositol cycle for the engulfment of C3bi-opsonized particles. Despite a total lack of receptor-induced formation of inositol phosphates, a significantly increased accumulation of diacylglycerol accompanied the ingestion of C3bi-opsonized particles. These data show that the engulfment of C3bi-opsonized particles can occur independently of both a calcium transient and an increased inositol phosphate production. However, the observed accumulation of diacylglycerol, not derived from phosphoinositides, suggests that this second messenger play a role in the control of the engulfment process.

Inhibition of fMLP-triggered respiratory burst of human monocytes by adenosine: involvement of A3 adenosine receptor

“…It was demonstrated that cAMP (via PKA activation) inhibited G-proteins [34], phospholipase C [35], inositol 1,4,5-triphosphate generation [35,36], formation of diacylglycerol [37], and release of Ca 2ϩ from intracellular storage organelles [36,38]. In this study, the failure of Ado to inhibit fMLPinduced Ca 2ϩ increase suggests that neither PLC-activated Ca 2ϩ release nor diacylglycerol (DAG) formation explains the reduction in O 2 Ϫ generation induced by fMLP.…”

An Essential Role of STIM1, Orai1, and S100A8–A9 Proteins for Ca2+ Signaling and FcγR-Mediated Phagosomal Oxidative Activity

“…On the one hand, some studies have shown that the ingestion of insoluble immune complex mediated by FcgR was independent of IP 3 (23). On the other hand, IP 3 production has been found to be concomitant with FcgR activation (22,23). This discordance could be explained by the fact that IP 3 involvement in FcgR-mediated phagocytosis varies according to the cell type studied and the subclasses of FcgR activated by a given stimulus (insoluble immune complex or zymosan bioparticles).…”

“…In addition, IP 3 production has been associated with the mechanism of phagocytosis (21,22). In contrast, Rosales and Brown (23) excluded a role for the IP 3 pathway in FcgR-mediated particle internalization.…”

Cholesterol-modulating Agents Selectively Inhibit Calcium Influx Induced by Chemoattractants in Human Neutrophils

“…Their occupancy results in the G protein-dependent activation of several signaling pathways (PLC ␤ , adenylate cyclase, tyrosine phosphorylation) that lead to the generation of multiple second messengers including transient increases in the level of cytoplasmic free calcium (5,6). These are known to be involved in the initiation and modulation of several critical neutrophil responses including phagocytosis (7)(8)(9) and the activation of the NADPH oxidase (10 -12).…”