Respiratory syncytial virus stimulates neutrophil degranulation and chemokine release.
Neutrophil infiltration of the airways is a common finding in respiratory syncytial virus (RSV) bronchiolitis. Neutrophil-derived chemokines and neutrophil granule contents can cause further inflammation, hyperresponsiveness, and damage of the airways. In this study, peripheral blood neutrophils incubated with RSV (multiplicity of infection (MOI) = 10) induced IL-8, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and myeloperoxidase (MPO) release. In contrast, LPS induced only chemokine but not MPO release. RSV-induced chemokine and MPO release was noncytotoxic as assessed by trypan blue exclusion. The mechanism of RSV-induced chemokine release was shown to be transcription dependent since cytokine mRNA synthesis was increased with RSV stimulation and the process was inhibited by actinomycin-D. In addition, the effect of dexamethasone (dex) on mediator release was also studied. Dex significantly inhibited chemokine release but did not inhibit MPO release. The mechanism of inhibition of the release of these chemokines is probably posttranscriptional since the mRNA synthesis was not inhibited by dex. We conclude that the release of chemokines (IL-8, MIP-1alpha, MIP-1beta) and granule enzymes (MPO) by RSV-stimulated neutrophils may contribute to the pulmonary pathology in RSV bronchiolitis. These in vitro findings showing that dex failed to consistently inhibit all the RSV-induced release of neutrophil inflammatory mediators may explain the variable efficacy of corticosteroids in the treatment of RSV bronchiolitis.
Jaovisidha
P
P
Department of Immunology/Microbiology, Rush Medical College, Chicago, IL 60612, USA.
Peeples
M E
ME
Brees
A A
AA
Carpenter
L R
LR
Moy
J N
JN
D000328:Adult; D015550:Cell Degranulation / Q000276:immunology*; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
D018925:Chemokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D003907:Dexamethasone