Anaphylactic reaction induced by Toxoplasma gondii-derived heat shock protein 70.
Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) is a virulent molecule specific for tachyzoites of T. gondii. The expression of T.g.HSP70 rapidly increases just before death of the host, indicating that T.g.HSP70 functions as a danger signal during lethal acute T. gondii infection. In the present study, T.g.HSP70 was proven to be capable of inducing lethal anaphylactic reaction in T. gondii-infected wild-type (WT) mice. Anaphylactic reaction appeared within the first hour after intraperitoneal injection of T.g.HSP70 and was characterized by a series of consequent symptoms until death. T.g.HSP70-induced anaphylactic reaction was not observed in IFN-gamma knockout (GKO) mice, indicating the involvement of IFN-gamma in the reaction. The anaphylactic reaction was transferable to GKO mice by splenocytes but not serum from infected WT mice. Also, this reaction occurred in B cell-deficient mice, indicating that T.g.HSP70-induced anaphylactic reaction occurred through an Ig-independent pathway. The messenger RNA (mRNA) expression of IFN-gamma increased significantly in splenocytes from T. gondii-infected WT mice after T.g.HSP70 injection. Furthermore, the mRNA expression of platelet-activating factor (PAF) acetylhydrolase in WT, but not GKO mice, distinctly increased during the occurrence of T.g.HSP70-induced anaphylactic reaction, indicating the involvement of PAF in T.g.HSP70-induced anaphylactic reaction. Treatment with PAF receptor antagonist rescued WT mice from the anaphylactic reaction. These data demonstrated the involvement of IFN-gamma-dependent PAF activation in T.g.HSP70-induced anaphylactic reaction.
Fang
Hao
H
Department of Infection and Host Defense, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Aosai
Fumie
F
Mun
Hye-Seong
HS
Norose
Kazumi
K
Ahmed
Azza Kamal
AK
Furuya
Mitsuko
M
Yano
Akihiko
A
D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D007371:Interferon-gamma / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology / Q000494:pharmacology / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D018840:HSP70 Heat-Shock Proteins; D010972:Platelet Activating Factor; D015800:Protozoan Proteins; D011726:Pyridinium Compounds; C053321:CV 6209; D007371:Interferon-gamma