INTERACTION OF STAPHYLOCOCCUS-AUREUS WITH HUMAN NEUTROPHILS AND THE DOWN-REGULATION OF TNF RECEPTORS

Citation
A. Ferrante et al., INTERACTION OF STAPHYLOCOCCUS-AUREUS WITH HUMAN NEUTROPHILS AND THE DOWN-REGULATION OF TNF RECEPTORS, The Journal of immunology, 152(8), 1994, pp. 3998-4004
Citations number
35
Categorie Soggetti
Immunology
Journal title
The Journal of immunology
ISSN journal
00221767 → ACNP
Volume
152
Issue
8
Year of publication
1994
Pages
3998 - 4004
Database
ISI
SICI code
0022-1767(1994)152:8<3998:IOSWHN>2.0.ZU;2-M
Abstract
We have shown previously that pre-exposure of neutrophils to TNF signi ficantly enhanced their killing of opsonized Staphylococcus aureus. We now demonstrate that the ability of TNF to enhance the bactericidal a ctivity is dependent on preincubation time; enhancement was still evid ent when TNF and bacteria were added simultaneously to neutrophils but if TNF addition was delayed by 5 min, no enhancement was seen. Eviden ce is presented that suggests that this could be related to a down-reg ulation 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 typ e B (55 kDa) receptor (htr-9), it was found that the expression of bot h receptors was decreased following treatment with the bacteria. The t ime course of lass of these receptors showed that the surface expressi on 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 n eutrophils showed essentially no change in the binding of radiolabeled tripeptide FMLP and, if anything, an increase in the expression of th e CD11b Ag (CR3 receptor). When another phagocytic stimulus was used, opsonized fungi (Torulopsis glabrata), a similar depression of TNF bin ding was also found, but opsonized sheep erythrocytes had no effect on the TNF binding, suggesting that the effects on the TNF receptor cann ot be explained simply on the basis of particle phagocytosis.