Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses

TY - JOUR

T1 - Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses

AU - van der Plas, Mariena J A

AU - van der Does, Anne M

AU - Baldry, Mara

AU - Dogterom-Ballering, Heleen C M

AU - van Gulpen, Co

AU - van Dissel, Jaap T

AU - Nibbering, Peter H

AU - Jukema, Gerrolt N

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - Animals

KW - Anti-Inflammatory Agents

KW - Antigens, CD11b

KW - Antigens, CD18

KW - Calcium

KW - Candida albicans

KW - Cyclic AMP

KW - Diptera

KW - Humans

KW - Hydrogen Peroxide

KW - Larva

KW - N-Formylmethionine Leucyl-Phenylalanine

KW - Neutrophils

KW - Pancreatic Elastase

KW - Phagocytosis

KW - Wound Healing

U2 - 10.1016/j.micinf.2007.01.008

DO - 10.1016/j.micinf.2007.01.008

M3 - Journal article

C2 - 17350304

SN - 1286-4579

VL - 9

SP - 507

EP - 514

JO - Microbes and Infection

JF - Microbes and Infection

IS - 4

ER -