A SYNTHETIC TUMOR-NECROSIS-FACTOR-ALPHA AGONIST PEPTIDE ENHANCES HUMAN POLYMORPHONUCLEAR LEUKOCYTE-MEDIATED KILLING OF PLASMODIUM-FALCIPARUM IN-VITRO AND SUPPRESSES PLASMODIUM-CHABAUDI INFECTION IN MICE

Citation
Lm. Kumaratilake et al., A SYNTHETIC TUMOR-NECROSIS-FACTOR-ALPHA AGONIST PEPTIDE ENHANCES HUMAN POLYMORPHONUCLEAR LEUKOCYTE-MEDIATED KILLING OF PLASMODIUM-FALCIPARUM IN-VITRO AND SUPPRESSES PLASMODIUM-CHABAUDI INFECTION IN MICE, The Journal of clinical investigation, 95(5), 1995, pp. 2315-2323
Citations number
40
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
00219738
Volume
95
Issue
5
Year of publication
1995
Pages
2315 - 2323
Database
ISI
SICI code
0021-9738(1995)95:5<2315:ASTAPE>2.0.ZU;2-C
Abstract
A peptide corresponding to residues 70-80 of the TNF-alpha polypeptide was synthesized and shown to enhance human PMN-mediated killing of Pl asmodium falciparum in vitro and reduced the Plasmodium chabaudi paras itemia in mice. Studies of the mechanism of action showed that the pep tide, TNF(70-80), stimulated and primed PMN for an increased respirato ry burst and release of granule constituents in response to a second a gonist, The PMN-stimulatory activity of the peptide was inhibited by m Abs against the p55 and p75 TNF receptors and a TNF-neutralizing mAb, Analysis of PMN receptor expression showed that CR3 (CD18/CD11b) and F c gamma RIII were upregulated by TNF(70-80), which was consistent with the peptide's ability to enhance parasite killing by PMN. The peptide , unlike TNF, did not increase the expression of adhesion molecules on endothelial cells and failed to promote binding of P, falciparum-infe cted erythrocytes to endothelial cells, TNF(70-80) also inhibited the TNF-induced increase in adhesion of P, falciparum-infected erythrocyte s to endothelial cells. The results demonstrate that the host-protecti ve effects of TNF can be retained while toxic effects are eliminated u sing a selected, characterized subunit of the cytokine.