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The ability of polymorphonuclear leukocyte priming agents to overcome influenza A virus-induced cell dysfunction
J S Abramson1, M P Wagner, E P Ralston
1Department of Pediatrics, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Abstract:
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.
Insights
Influenza A virus impairs immune cells called polymorphonuclear leukocytes (PMNLs), increasing secondary bacterial infection risk. Compounds like GM-CSF, GTP, and OAG can restore PMNL function, potentially treating these infections.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Influenza virus infections often lead to severe secondary bacterial infections.
- These infections are linked to influenza-induced suppression of polymorphonuclear leukocyte (PMNL) function.
- Restoring PMNL function is crucial for combating these secondary infections.
Purpose of the Study:
- To investigate if priming agents can counteract influenza A virus (IAV)-induced PMNL dysfunction.
- To determine if compounds can restore PMNL chemiluminescence response to stimuli after IAV infection.
Main Methods:
- Assessing the ability of granulocyte-macrophage colony stimulating factor (GM-CSF), guanosine triphosphate (GTP), and 1-oleoyl-2-acetylglycerol (OAG) to prime PMNLs.
- Measuring PMNL chemiluminescence response to N-formylmethionyl-leucylphenylalanine (FMLP) and phorbol 12-myristate 13-acetate (PMA) after IAV exposure.
- Correlating the extent of PMNL priming with the ability to overcome virus-induced dysfunction.
Main Results:
- GM-CSF, GTP, and OAG demonstrated PMNL priming capabilities.
- These compounds partially or fully restored IAV-impaired PMNL function.
- A direct correlation existed between the degree of PMNL priming and the restoration of function.
Conclusions:
- Priming agents like GM-CSF, GTP, and OAG can overcome IAV-induced PMNL dysfunction.
- These findings suggest potential therapeutic strategies for secondary bacterial infections following influenza.
- Understanding the mechanism of priming may lead to novel treatments for influenza-associated complications.