RT Journal
A1 Johnson JL, Moore EE, Patrick DA, et al
T1 EXtracellular signal-related kinase 1/2 and p38 mitogen-activated protein kinase pathways serve opposite roles in neutrophil cytotoxicity
JF Archives of Surgery
JO Archives of Surgery
YR 1999
FD October 1
VO 134
IS 10
SP 1074
OP 1078
DO 10.1001/archsurg.134.10.1074
UL http://dx.doi.org/10.1001/archsurg.134.10.1074
AB Background 
    Inflammatory stimuli rapidly activate mitogen-activated protein kinases (MAPKs) in neutrophils (PMNs). However, their role in cytotoxic function remains unknown. Elucidating the signals involved in release of cytotoxic agents from PMNs may provide new avenues for therapy in diseases of diminished or excessive PMN function.Hypothesis 
    The p38 MAPK and extracellular signal-related kinase 1/2 (ERK1/2) modulate superoxide generation and elastase release in activated human PMNs.Study Design 
    Isolated human PMNs were incubated with specific inhibitors of MAPK pathways, or vehicle control solution, before activation with the bacterial peptide f-Met-Leu-Phe.Main Outcome Measures 
    The rate of superoxide release from activated PMNs was measured by the superoxide dismutase–inhibitable reduction of cytochrome-c. Elastase release from PMNs was determined by cleavage of the substrate Ala-Ala-Pro-Val-pNA.Results 
    Superoxide release from activated PMNs was inhibited by blockade of p38 MAPK activation but unaffected by blockade of ERK1/2. Conversely, elastase release was unaffected by p38 MAPK inhibition and increased by ERK1/2 inhibition.Conclusions 
    Activation of p38 MAPK promotes superoxide release from PMNs activated by f-Met-Leu-Phe. The ERK1/2 pathway may serve as a negative feedback mechanism for granule exocytosis.