title: Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses.
abstract: There is renewed interest in the use of maggots (Lucilia sericata) to aid in healing of chronic wounds. In such wounds neutrophils precipitate tissue damage rather than contribute to healing. As the molecules responsible for the beneficial actions of maggots are contained in their excretions/secretions (ES), we assessed the effects of ES on functional activities of human neutrophils. ES dose-dependently inhibited elastase release and H(2)O(2) production by fMLP-activated neutrophils; maximal inhibition was seen with 5-50 microg of ES/ml. In contrast, ES did not affect phagocytosis and intracellular killing of Candida albicans by neutrophils. Furthermore, 0.5 microg of ES/ml already inhibited neutrophil migration towards fMLP. ES dose-dependently reduced the fMLP-stimulated expression of CD11b/CD18 by neutrophils, suggesting that ES modulate neutrophil adhesion to endothelial cells. ES did not affect the fMLP-induced rise in [Ca(2+)](i) in neutrophils, indicating that ES act down-stream of phospholipase C-mediated activation of protein kinase C. In agreement, ES inhibited PMA-activated neutrophil functional activities. ES induced a rise in intracellular cAMP concentration in neutrophils and pharmacological activators of cAMP-dependent mechanisms mimicked their inhibitory effects on neutrophils. The beneficial effects of maggots on chronic wounds may be explained in part by inhibition of multiple pro-inflammatory responses of activated neutrophils by ES.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Mariena J A
authors.initials: MJ
authors.lastname: van der Plas
authors.forename: Anne M
authors.initials: AM
authors.lastname: van der Does
authors.forename: Mara
authors.initials: M
authors.lastname: Baldry
authors.forename: Heleen C M
authors.initials: HC
authors.lastname: Dogterom-Ballering
authors.forename: Co
authors.initials: C
authors.lastname: van Gulpen
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Peter H
authors.initials: PH
authors.lastname: Nibbering
authors.forename: Gerrolt N
authors.initials: GN
authors.lastname: Jukema
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000096:biosynthesis / Q000276:immunology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology; D000242:Cyclic AMP / Q000378:metabolism; D004175:Diptera / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007814:Larva; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D010196:Pancreatic Elastase / Q000097:blood / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D018821:CD18 Antigens; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D010196:Pancreatic Elastase; D002118:Calcium