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
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
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.