Differential induction of membrane-associated interleukin 1 (IL-1) expression and IL-1 alpha and IL-1 beta secretion by lipopolysaccharide and silica in human monocytes.
Bacterial lipopolysaccharide (LPS) and silica dust are known to be effective inducers of interleukin 1 (IL-1) in human cultured monocytes. The data reported here show that although the levels of secreted IL-1 were equally high after in vitro stimulation with an optimal dose of LPS or silica, there were two clear differences: (i) the levels of membrane-associated IL-1 (as detected by the comitogenic effect of paraformaldehyde (PFA)-fixed cells or purified membrane fragments on murine thymocytes) were ca. five times higher after LPS stimulation than after silica stimulation, (ii) the secreted IL-1 after LPS stimulation was mainly of the pI 7 (IL-1 beta) type, while after silica stimulation there were equally high amounts of pI 7 and pI 5 (i.e. IL-1 alpha) forms. In both cases the IL-1 active molecules belonged to the 15 kDa class. These data show that the nature of the activating agent has a clear influence on the distribution of the biologically active IL-1 molecules. Moreover, the finding that after silica stimulation the amount of membrane-associated IL-1 (which was recently shown to be of the IL-1 alpha type) was low, while IL-1 alpha in the culture fluid was clearly elevated, suggests that the IL-1 alpha not attached to the cell membrane (or released from it) significantly contributes to the secreted IL-1 pool.
Hurme
M
M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Seppälä
I J
IJ
D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D007526:Isoelectric Point; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008970:Molecular Weight; D009000:Monocytes / Q000502:physiology*; D012822:Silicon Dioxide / Q000494:pharmacology*; D012995:Solubility
D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012822:Silicon Dioxide