Abstract
Background: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T-cell responses in the absence of adjuvants. Methods: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T-cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA-adducted proteins was also investigated. Results: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T-cell proliferative responses after immunization with HEL-MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL-MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL-MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL-MAA were class II positive, indicating that antigen-presenting cells can bind the MAA-adducted HEL, and potentially initiate immune responses. Conclusions: MAA modification of proteins induces antibody and T-cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA-adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 94-106 |
| Number of pages | 13 |
| Journal | Alcoholism: Clinical and Experimental Research |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2002 |
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Keywords
- Adducts
- Aldehydes
- Autoimmunity
- Immune Responses
- Scavenger Receptors
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Toxicology
- Psychiatry and Mental health
Cite this
Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation. / Willis, Monte S.; Klassen, Lynell Warren; Tuma, Dean J.; Sorrell, Michael Floyd; Thiele, Geoffrey Milton.
In: Alcoholism: Clinical and Experimental Research, Vol. 26, No. 1, 01.01.2002, p. 94-106.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Adduction of soluble proteins with malondialdehyde-acetaldehyde (MAA) induces antibody production and enhances T-cell proliferation
AU - Willis, Monte S.
AU - Klassen, Lynell Warren
AU - Tuma, Dean J.
AU - Sorrell, Michael Floyd
AU - Thiele, Geoffrey Milton
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Background: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T-cell responses in the absence of adjuvants. Methods: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T-cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA-adducted proteins was also investigated. Results: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T-cell proliferative responses after immunization with HEL-MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL-MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL-MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL-MAA were class II positive, indicating that antigen-presenting cells can bind the MAA-adducted HEL, and potentially initiate immune responses. Conclusions: MAA modification of proteins induces antibody and T-cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA-adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.
AB - Background: The alcohol metabolites malondialdehyde and acetaldehyde can combine to form stable adducts (MAA) which are found in the livers of humans and rats after significant alcohol ingestion. While adducted proteins induce antibody responses in the absence of adjuvants, the mechanisms by which these responses occur are unknown. Thus, it was the purpose of these studies to investigate how MAA modification stimulates antibody and T-cell responses in the absence of adjuvants. Methods: Hen egg lysozyme (HEL) was modified with increasing levels of MAA and was used as an immunogen, and antibody and T-cell responses were determined. The role of scavenger receptors in the immunogenicity of MAA-adducted proteins was also investigated. Results: Maximum antibody response was induced after immunization with 1.8 nM MAA/nM HEL, and was primarily an IgG1 response to HEL as determined by inhibition ELISAs. T-cell proliferative responses after immunization with HEL-MAA were solely to HEL. Immunization with a scavenger receptor ligand in conjunction with HEL-MAA increased the predominant IgG1 response and sharply decreased the IgG2a response by approximately 50%. Binding of HEL-MAA by splenocytes was determined by flow cytometry to be approximately 15% greater than HEL alone, showing a doubling of the geometric mean fluorescence. Also, most of the cells that bound HEL-MAA were class II positive, indicating that antigen-presenting cells can bind the MAA-adducted HEL, and potentially initiate immune responses. Conclusions: MAA modification of proteins induces antibody and T-cell proliferative responses in vivo. Initial studies suggest that these responses may be mediated by scavenger receptors that recognize MAA-adducted proteins. This suggests a mechanism by which proteins modified with oxidative products associated with chronic ethanol consumption may alter immune responses that may play an active role in the development and/or progression of alcoholic liver disease.
KW - Adducts
KW - Aldehydes
KW - Autoimmunity
KW - Immune Responses
KW - Scavenger Receptors
UR - http://www.scopus.com/inward/record.url?scp=0036148631&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036148631&partnerID=8YFLogxK
U2 - 10.1111/j.1530-0277.2002.tb02436.x
DO - 10.1111/j.1530-0277.2002.tb02436.x
M3 - Article
C2 - 11821659
AN - SCOPUS:0036148631
VL - 26
SP - 94
EP - 106
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
SN - 0145-6008
IS - 1
ER -