Role of protein kinase C alpha for uptake of unopsonized prey and phagosomal maturation in macrophages |
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Authors: | Holm A Tejle K Gunnarsson T Magnusson K-E Descoteaux A Rasmusson B |
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Affiliation: | Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Link?ping University, S-581 85 Link?ping, Sweden. asa.holm@imk.lu.se |
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Abstract: | Protein kinase C alpha (PKC alpha) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the disassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKC alpha. To investigate a possible connection between PKC alpha and LPG's effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PCK alpha (DN PKC alpha). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKC alpha-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKC alpha is involved in F-actin turnover in macrophages and that PKC alpha-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKC alpha by LPG. |
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Keywords: | PKCα Actin Phagocytosis Macrophage Lipophosphoglycan |
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