Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.

Details

Serval ID
serval:BIB_1AEB525DF4DD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Analysis of cytokine immune response profile in response to inflammatory stimuli in mice with genetic defects in fetal and adult hemoglobin chain expression.
Journal
The pharmacogenomics journal
Author(s)
Khatri I., Alexander C., Brandenburg K., Chen Z., Heini A., Heumann D., Mach J.P., Mazzoli V., Rietschel E., Terskikh A., Ulmer A., Yu K., Zähringer U., Gorczynski R.
ISSN
1473-1150 (Electronic)
ISSN-L
1470-269X
Publication state
Published
Issued date
07/2018
Peer-reviewed
Oui
Volume
18
Number
4
Pages
546-555
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice. To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, Hgbβ <sub>ma</sub> KO or Hgbβ <sub>mi</sub> KO. Hgbβ <sub>mi</sub> is the most prominent fetal Hgbβ chain, with Hgbβ <sub>ma</sub> more prominent in adult mice. Mice lacking another fetal Hgb chain, HgbεKO, died in utero. CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes. Splenocytes from Hgbβ <sub>ma</sub> KO mice stimulated in vitro with Conconavalin A showed a higher IL-2:IL-4 ratio than cells from Hgbβ <sub>mi</sub> KO mice. Following immunization in vivo with ovalbumin in alum, Hgbβ <sub>ma</sub> KO mice produced less IgE than Hgbβ <sub>mi</sub> KO mice, suggesting that in the absence of Hgbβ <sub>mi</sub> KO mice had a predeliction to heightened allergic-type responses. Using CHO cells transfected with cloned Hgb chains, we found that only the fetal Hgb chain, Hgbε, was secreted at high levels. Secretion of Hgbβ <sub>ma</sub> or Hgbβ <sub>mi</sub> chains was seen only after genetic mutation to introduce the two N-linked glycosylation sites present in Hgbε, but absent in the Hgbβ chains. We speculated that a previously unanticipated biological function of a naturally secreted fetal Hgb chain may be partly responsible for the effects reported following injection of animals with fetal, not adult, Hgb. Mice receiving injections of rabbit anti-Hgbε but not either anti-Hgbβ <sub>ma</sub> or anti-Hgbβ <sub>mi</sub> from day 14 gestation also showed a bias towards the higher IL-2:IL-4 ratios seen in Hgbβ <sub>mi</sub> KO mice.
Keywords
Animals, CHO Cells, Cricetinae, Cricetulus, Cytokines/immunology, Fetal Hemoglobin/administration & dosage, Fetal Hemoglobin/immunology, Fetus/immunology, Glutathione/immunology, Hemoglobins/genetics, Hemoglobins/immunology, Humans, Immunity, Innate, Liver Extracts/administration & dosage, Liver Extracts/immunology, Mice, Mice, Knockout, Sheep/immunology, Spleen/cytology
Pubmed
Web of science
Create date
22/01/2018 12:40
Last modification date
20/08/2019 13:51
Usage data