Interaction of Staphylococcus aureus with human neutrophils and the down-regulation of TNF receptors.
We have shown previously that pre-exposure of neutrophils to TNF significantly enhanced their killing of opsonized Staphylococcus aureus. We now demonstrate that the ability of TNF to enhance the bactericidal activity is dependent on preincubation time; enhancement was still evident when TNF and bacteria were added simultaneously to neutrophils but if TNF addition was delayed by 5 min, no enhancement was seen. Evidence is presented that suggests that this could be related to a down-regulation of TNF receptors by the bacteria, but in addition, the release of TNF receptor fragments may contribute to the inhibition observed. Scatchard analyses demonstrated a decrease from approximately 3000 TNF receptor (receptor binding) sites per cell to 450 following treatment with S. aureus, but essentially no change in receptor affinity. Using mAb directed against the type A (75 kDa) receptor (utr-1) and the type B (55 kDa) receptor (htr-9), it was found that the expression of both receptors was decreased following treatment with the bacteria. The time course of loss of these receptors showed that the surface expression of both molecules was markedly decreased by 5 min which correlated with the loss in ability of TNF to enhance the bactericidal activity. In contrast to changes seen in the binding of TNF, similarly treated neutrophils showed essentially no change in the binding of radiolabeled tripeptide FMLP and, if anything, an increase in the expression of the CD11b Ag (CR3 receptor). When another phagocytic stimulus was used, opsonized fungi (Torulopsis glabrata), a similar depression of TNF binding was also found, but opsonized sheep erythrocytes had no effect on the TNF binding, suggesting that the effects on the TNF receptor cannot be explained simply on the basis of particle phagocytosis.
Ferrante
A
A
Department of Immunology, Women's and Children's Hospital, Australia.
Martin
A J
AJ
Bates
E J
EJ
Kowanko
I C
IC
Harvey
D P
DP
Parsons
D
D
Rathjen
D A
DA
Russ
G
G
Dayer
J M
JM
D015536:Down-Regulation; D006801:Humans; D008970:Molecular Weight; D009504:Neutrophils / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D016897:Respiratory Burst; D013211:Staphylococcus aureus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha