Comparison of influenza A virus and formyl-methionyl-leucyl- phenylalanine
activation of the human neutrophil
KL Hartshorn, DE Daigneault, MR White, M Tuvin, JL Tauber and AI Tauber
Department of Medicine, Boston City Hospital, MA.
Influenza A virus (IAV) activates the human neutrophil, but induces a
dysfunctional state as well. Cell activation may contribute to the
containment of the virus and/or cause local tissue damage. Certain features
of the neutrophil activation response elicited by IAV are distinctive when
compared with that triggered by formyl-methyl-leucyl- phenylalanine (FMLP).
An atypical respiratory burst response occurs in which hydrogen peroxide,
but no superoxide, is formed. This unusual respiratory burst stoichiometry
persists despite marked priming of the IAV-induced response. A
comprehensive examination of the activation cascade initiated by these
stimuli failed to show an explanation for these differences. Both IAV and
FMLP comparably stimulate inositol trisphosphate and phosphatidic acid
production. The subsequent increase in intracellular calcium (Ca2+i) upon
FMLP stimulation was more dependent on extracellular Ca2+ than with IAV
activation, but both stimuli induced Ca2+ influx. FMLP and IAV exhibited
equal susceptibility to inhibition by protein kinase inhibitors in
eliciting the respiratory burst, and actin polymerization occurred in
response to each agonist. A possible explanation for the anomalous
respiratory burst induced by IAV is that O2- is generated at an
intracellular site inaccessible to assay, and/or virus binding to sialic
acid constituents of the plasma membrane alters the O2- generating capacity
of the respiratory burst oxidase; evidence for each mechanism is offered.
Volume 79,
Issue 4,
pp. 1049-1057,
02/15/1992
Copyright © 1992 by The American Society of Hematology
