The ability of polymorphonuclear leukocyte priming agents to overcome influenza A virus-induced cell dysfunction.
The major mortality and morbidity resulting from influenza virus infections are due to secondary bacterial infections which occur in association with virus-induced inhibition of polymorphonuclear leukocyte (PMNL) function. The present study was undertaken to determine if compounds which prime PMNL function to subsequent stimulation with N-formylmethionyl-leucylphenylalanine (FMLP) or phorbol 12-myristate 13-acetate (PMA) can overcome influenza A virus (IAV)-induced inhibition of the PMNL chemiluminescence response to these stimuli. Granulocyte-macrophage colony stimulating factor (GM-CSF), guanosine triphosphate (GTP), and 1-oleoyl-2-acetylglycerol (OAG) were able to prime the PMNL response to FMLP and/or PMA and totally or partially overcome IAV-induced PMNL dysfunction in cells stimulated with FMLP or PMA. A direct correlation was found between the extent of PMNL priming due to GM-CSF, GTP, and OAG and the capacity of these compounds to overcome virus-induced PMNL dysfunction. The implications of these findings in regard to the mechanism by which priming agents overcome IAV-induced cell dysfunction and the potential of these compounds as therapeutic agents to treat secondary bacterial infections are discussed.
Abramson
J S
JS
Department of Pediatrics, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Wagner
M P
MP
Ralston
E P
EP
Wei
Y
Y
Wheeler
J G
JG
D004075:Diglycerides / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology*; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000494:pharmacology
D004075:Diglycerides; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006160:Guanosine Triphosphate; C038237:1-oleoyl-2-acetylglycerol; D013755:Tetradecanoylphorbol Acetate