Lipopolysaccharide- and interferon-gamma-induced expression of hck and lyn tyrosine kinases in murine bone marrow-derived macrophages.
We have examined the role of tyrosine phosphorylation during the course of macrophage activation. Initial experiments indicated that vanadate, a known phosphotyrosine phosphatase inhibitor, enhanced the phorbol 12-myristate 13-acetate (PMA)-triggered respiratory burst and potentiated the priming effects of bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), suggesting that tyrosine phosphorylation may be important in these end cell functions. As src-related kinases have been implicated in the activation of cells of other haemopoietic lineages, we examined the relationship between the activity of two such kinases, hck and lyn, and priming of the respiratory burst. We found that the level of hck and lyn is increased following exposure of bone marrow-derived macrophages (BMM) to LPS or IFN-gamma. The induction of both of these kinases follows similar kinetics with maximal activity occurring at 24-48 h. Interestingly, the kinetics of induction of hck and lyn kinase activity in BMM demonstrated a close temporal relationship with the priming effects of LPS and IFN-gamma on the macrophage respiratory burst. Collectively, these observations raise the possibility that modulation of expression of hck and lyn is involved in the regulation of the respiratory burst.
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Royal Melbourne Hospital, Victoria, Australia.
I
I
Boulet
S
S
Ralph
E
E
Stanley
P
P
Lock
A R
AR
Dunn
S P
SP
Green
W A
WA
Phillips
D000818:Animals; D001854:Bone Marrow Cells; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck; D012333:RNA, Messenger / Q000235:genetics; D016897:Respiratory Burst; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D019061:src-Family Kinases
D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019000:Phosphotyrosine; D014638:Vanadates; D014443:Tyrosine; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C496632:Hck protein, mouse; D051572:Proto-Oncogene Proteins c-hck; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases