title: Hydrophobic but not hydrophilic statins enhance phagocytosis and decrease apoptosis of human peripheral blood cells in vitro.
abstract: The engulfing ability of phagocyting cells is related to the fluidity of the cell membrane that in turn depends on its chemical composition. Changes in membranal lipid content may increase or decrease membranal fluidity with a subsequent enhanced or impaired phagocytosis, respectively. Statins are recognized as potent inhibitors of cholesterol synthesis and therefore, are successfully administered to patients with hypercholesterolemia. Since it is considered that cholesterol affects cell function via changes in membrane composition, the present study was designed to examine the in vitro effect of three hydrophobic statins--atorvastatin, lovastatin and simvastatin, and a hydrophilic one--pravastatin, on the engulfing capacity, phagocytic index and apoptosis of peripheral blood phagocytes from healthy volunteers. Peripheral white blood cells obtained from 20 healthy normocholesterolemic individuals were incubated for 2h with 10 and 50 microM of the four statins and phagocytosis of fluorescent latex particles was detected by flow cytometry. Apoptosis was examined using annexin V and propidium iodide staining. An increase in the percentage of phagocyting cells was observed after incubation with 50 microM of lovastatin and simvastatin. On the other hand, all three hydrophobic statins induced a dose-dependent increase in the phagocytic index. The hydrophilic pravastatin did not affect phagocytosis, phagocytic index and apoptosis. All three hydrophobic statins at 50 microM exerted a slight, but significant decrease of apoptosis. The results suggest that the effect of hydrophobic statins on the engulfing capacity of human peripheral blood phagocytes and apoptosis is dependent on their dosage and physiochemical properties. This observation is an additional contribution to the statins' pleiotropic effect.
authors.affiliation: Department of Medicine C, Rabin Medical Center, Hasharon Hospital, the Sackler School of Medicine, Tel Aviv University, 7 Keren Kayemet Street, Petah Tiqva, Israel.
authors.forename: Hertzel
authors.initials: H
authors.lastname: Salman
authors.forename: Michael
authors.initials: M
authors.lastname: Bergman
authors.forename: Meir
authors.initials: M
authors.lastname: Djaldetti
authors.forename: Hanna
authors.initials: H
authors.lastname: Bessler
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008148:Lovastatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D017035:Pravastatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D019821:Simvastatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin