Two Chromogranin A-Derived Peptides Induce Calcium Entry in Human Neutrophils by Calmodulin-Regulated Calcium Independent Phospholipase A2

Stress and infection lead to two different pathways for stimulation of PMN secretion, by release of CgA and CgA-derived peptides from the adrenal medulla, as indicated by 1a–6a (black), and by PVL leucocidin stimulation by S. aureus infections, as indicated by 1b–3b (grey), respectively. Abbreviated symbols: P (CHR, CAT), P' (CAT), CPP (Cell Penetrating Peptide), CaM (calmodulin), iPLA2 (calcium independent phospholipase A2) LysoPL (lysophospholipids); GC (Golgi complex); PVL (Panton-Valentine leucocidin), R (receptor). The stress-stimulated pathway leads to penetration of P into the cytoplasm (2a), resulting in removal of inhibitory CaM, activation of iPLA2 to produce LysoPL (3a) and activation of Ca2+ influx through SOC (4a), converging on activated docking of secretory granules (5a) and subsequent release of proteins of relevance for innate immunity (6a). The negative feedback induced by P' on nicotinic cholinergic receptor of chromaffin cell is also indicated (7a). The infective route leads to activation of the putative PVL receptor coupled to opening of Ca2+-channels and a rise in intracellular Ca2+ (3b) that converges on docking of secretory granules and subsequent secretion of proteins of relevance for innate immunity (6a). Transcription of CgA in response to stress and infection is also indicated. Insert.The alignment of the two P sequences (CHR and CAT) with that of Penetratin (Cell penetrating peptide, CPP).

Publication

Two Chromogranin A-Derived Peptides Induce Calcium Entry in Human Neutrophils by Calmodulin-Regulated Calcium Independent Phospholipase A2 . (2009) Dan Zhang, et al. PLoS One. 2009;4(2):e4501. Figure: F9. All organisms Drosophila melanogaster Homo sapiens

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