title: CD66b Overexpression and Loss of C5a Receptors as Surface Markers for Staphylococcus aureus-Induced Neutrophil Dysfunction.
abstract: Neutrophil granulocytes constitute the main component of innate immunity in the clearance of bacterial infections. However, during systemic inflammation, immunoparalysis may occur resulting in neutrophil dysfunction. This study presents a new in vitro model for analyzing the dysfunction of human peripheral blood neutrophils resulting from the interaction with Staphylococcus aureus components in whole blood. After induction of a massive complement activation by S. aureus supernatant, the neutrophils exhibit a reduced phagocytic capacity resulting in a dramatic reduction of the antibacterial activity similar to that of neutrophils isolated from septic patients. The number of phagocytozing neutrophils is drastically reduced as well as the phagocytic capacity designated by a significantly lower number of ingested microbes. This dysfunction correlates with the loss of complement component 5a receptor 1 from the neutrophil cell surface and can be further characterized by a C5a-induced CD66b overexpression. The presented in vitro model offers a new platform for preclinical testing of immunosuppressive drugs and delivers new information for the understanding of neutrophil dysfunctions under the conditions described.
authors.affiliation: Department of Dermatology, Philipps-Universität of Marburg, Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Federal Institute for Drugs and Medical Devices, L2 Biosafety Laboratory, Bonn, Germany.
authors.forename: Alva
authors.initials: A
authors.lastname: Brodesser
authors.affiliation: Gesundheitsamt des Kreises Düren, Düren, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schnitzler
authors.affiliation: Federal Institute for Drugs and Medical Devices, L2 Biosafety Laboratory, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grüger
authors.affiliation: Federal Institute for Drugs and Medical Devices, L2 Biosafety Laboratory, Bonn, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Federal Institute for Drugs and Medical Devices, Biostatistics Unit, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Zinserling
authors.affiliation: Federal Institute for Drugs and Medical Devices, L2 Biosafety Laboratory, Bonn, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Zündorf
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D015934:Complement C4a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D016897:Respiratory Burst; D013211:Staphylococcus aureus / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C038245:C3 protein, human; D039481:CD11b Antigen; C504120:CEACAM8 protein, human; D015815:Cell Adhesion Molecules; D003176:Complement C3; D058851:GPI-Linked Proteins; C509295:ITGAM protein, human; D044087:Receptor, Anaphylatoxin C5a; D015934:Complement C4a; D015936:Complement C5a