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Bacterial phagocytosis activates extracellular signal‐regulated kinase and p38 mitogen‐activated protein kinase cascades in human neutrophils
Author(s) -
McLeish Kenneth R.,
Klein Jon B.,
Coxon Patricia Y.,
Head Kimberly Z.,
Ward Richard A.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.64.6.835
Subject(s) - wortmannin , phagocytosis , calphostin c , ly294002 , p38 mitogen activated protein kinases , biology , mapk/erk pathway , calphostin , kinase , microbiology and biotechnology , protein kinase a , phosphatidylinositol
The hypothesis that bacterial phagocytosis by human polymorphonuclear neutrophils (PMNs) stimulates MAPK cascades that regulate respiratory burst activation was tested. Extracellular response kinase (ERK) and p38 kinase, but not c‐Jun NH2‐terminal kinase, activities were increased within 5 min of phagocytosis of plasma‐opsonized Staphylococcus aureus (S‐SA), reached maximum at 20–30 min, and remained elevated through 60 min. The role of Fcγ receptors was examined using gamma globulin‐opsonized SA (IgG‐SA), whereas CR3 receptors were activated by particulate β‐glucan. IgG‐SA stimulated a maximal ERK activity at 30 min, whereas p38 activity was maximal at 5 min. β‐glucan stimulated maximal ERK activity at 5 min and maximal p38 activity at 2 min. Non‐opsonized bacteria were ingested at 10% of the level of S‐SA and stimulated a minimal increase in ERK and p38 activity at 60 min. S‐SA stimulation of ERK was inhibited by wortmannin, LY294002, and genistein, but not calphostin C; whereas p38 stimulation was inhibited by calphostin C and genistein, but not wortmannin and LY294002. Simultaneous measurement of phagocytosis and H 2 O 2 production by flow cytometry was used to assess the role of ERKs and p38 kinase in phagocytosis. The MEK inhibitor PD098059 had no significant effect on phagocytosis or H 2 O 2 production. The p38 kinase inhibitor SB203580 significantly attenuated H 2 O 2 production, whereas phagocytosis was unaffected. In conclusion, bacterial phagocytosis stimulates ERK and p38 activation by distinct signal transduction pathways. Phagocytosis‐stimulated p38 kinase activity is necessary for optimal H 2 O 2 production. J. Leukoc. Biol. 64: 835–844; 1998.