Alpha-1-acid glycoprotein inhibits phorbol ester-induced but not Fc-receptor-induced generation of reactive oxygen species in bovine peripheral blood neutrophils.
Alpha-1-acid glycoprotein (AGP) is an acute-phase protein with anti-inflammatory and immunomodulating properties. AGP is described as a potent inhibitor of the production of reactive oxygen species (ROS) in human neutrophils. However, published reports about the mechanism of inhibition are conflicting. The influence of bovine AGP on the production of ROS by bovine peripheral blood polymorphonuclear leucocytes (PMN) was studied using a highly sensitive method approaching its inhibitory mechanism. ROS production in PMN was induced with phorbol 12-myristate 13-acetate (PMA) or opsonized Staphylococcus aureus bacteria. ROS generation was quantified and evaluated by flow cytometry. AGP efficiently suppressed PMA, but did not opsonize bacteria-induced ROS generation in vitro. The suppressive effect was concentration-dependent and adversely proportional to PMA concentration. The selective inhibitory potential of AGP in comparison with ovalbumin (OVA) and bovine serum albumin (BSA) showed that ROS inhibition was not a mere protein effect. ROS production was suppressed only if AGP and PMA were simultaneously present with PMN. Pre-incubation of PMN with AGP did not alter the PMN response to PMA. Moreover, AGP could not suppress ROS production after pre-stimulation of PMN with PMA. Human and bovine AGP did not differ in their inhibitory potential to the PMA-induced ROS production in bovine, human and equine PMN. The results show that AGP does not modulate bovine neutrophil functions directly, but acts as a scavenger of PMA.
Stakauskas
R
R
Laboratory of Immunology, Lithuanian Veterinary Academy, Kaunas, Lithuania. rimantas.stakauskas@tiho-hannover.de
Leibold
W
W
Pieskus
J
J
Mironova
L
L
Schuberth
H-J
HJ
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006736:Horses; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009895:Opsonin Proteins / Q000494:pharmacology; D009961:Orosomucoid / Q000008:administration & dosage / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011961:Receptors, Fc / Q000008:administration & dosage; D013211:Staphylococcus aureus / Q000187:drug effects / Q000276:immunology
D009895:Opsonin Proteins; D009961:Orosomucoid; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; D011961:Receptors, Fc