PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY IN THE MACROPHAGE IS ENHANCED BYLIPOPOLYSACCHARIDE, TUMOR-NECROSIS-FACTOR-ALPHA, AND GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR - CORRELATION WITH PRIMING OF THE RESPIRATORY BURST/
S. Bassal et al., PHOSPHOTYROSINE PHOSPHATASE-ACTIVITY IN THE MACROPHAGE IS ENHANCED BYLIPOPOLYSACCHARIDE, TUMOR-NECROSIS-FACTOR-ALPHA, AND GRANULOCYTE MACROPHAGE-COLONY STIMULATING FACTOR - CORRELATION WITH PRIMING OF THE RESPIRATORY BURST/, Biochimica et biophysica acta. Molecular cell research, 1355(3), 1997, pp. 343-352
Tyrosine phosphorylation is now recognised as a key event in the activ
ation of the macrophage respiratory burst. Since vanadate, a phosphoty
rosine phosphatase (PTP) inhibitor is able to enhance the respiratory
burst, we proposed that agents which prime the macrophage for enhance
respiratory burst activity may do so by suppressing cellular PTP activ
ity. The level of PTP activity in murine bane marrow-derived macrophag
es (BMM) was assessed by the ability of cell lysates to dephosphorylat
e P-32-labelled RR-src peptide. In contrast to our hypothesis, pretrea
tment of BMM with bacterial lipopolysaccharide (LPS), tumor necrosis f
actor alpha (TNF alpha) or granulocyte/macrophage-colony stimulating f
actor (GMCSF), agents which prime for enhanced respiratory burst activ
ity, was found to dramatically increase the level of cellular PTP acti
vity. The time-course for this increase correlated well with the time
course of priming by these agents. In addition, colony stimulating fac
tor-1, a cytokine which does not prime the macrophage respiratory burs
t, did not enhance PTP levels. The physiological relevance of the incr
eased PTP activity was further supported by confirming it was active a
gainst endogenous tyrosine phosphorylated substrates. Interestingly, p
horbol myristate acetate and zymosan, agents which trigger the macroph
age respiratory burst, were found to inhibit the PTP activity of BMM.
Our results demonstrate the regulation of cellular PTP activity by pri
ming agents and further highlight the importance of tyrosine phosphory
lation and dephosphorylation events in the regulation of macrophage fu
nction.