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Maternal immunization programs postnatal immune responses and reduces atherosclerosis in offspring
- Source :
- Circulation research, vol 99, iss 7, Circ Res
- Publication Year :
- 2006
- Publisher :
- eScholarship, University of California, 2006.
-
Abstract
- Maternal hypercholesterolemia during pregnancy increases offspring susceptibility to atherosclerosis by an oxidation-dependent mechanism. The present studies investigated whether maternal immunization with oxidized LDL (OxLDL) before pregnancy protects the fetus from atherogenic in utero programming by maternal hypercholesterolemia. Maternal immunization of NZW rabbits and LDL receptor–deficient mice indeed reduced atherosclerosis in adult offspring by up to 56%, but the protective effect could not be attributed to a reduction of fetal exposure to hypercholesterolemia alone, and even nonspecific immune stimulation with adjuvant only provided some protection. Unexpectedly, offspring of immunized mothers developed increased IgM antibodies to selective OxLDL epitopes and increased IgM-LDL immune complexes, compared with offspring of nonimmunized controls. Even naïve offspring of OxLDL-immunized mothers never exposed to postnatal hypercholesterolemia responded to a one-time OxLDL and KLH challenge with greater OxLDL-specific IgM responses, increased OxLDL-specific IgM-secreting B cells, and more IgM-LDL immune complexes. In contrast, maternal immunization with KLH, a T cell–dependent nonmammalian antigen, did not influence postnatal immune responses. Effects of maternal OxLDL-immunization on offspring B cells and selective antibodies were independent of transplacental passage of maternal immunoglobulins. Results show that maternal immunization with antigens prevalent in atherosclerotic lesions reduces atherogenesis in their offspring by mechanisms that include, but are not limited to, reduced fetal exposure to maternal hypercholesterolemia and lipid peroxidation. More importantly, they demonstrate in principle that maternal adaptive immunity to selective antigens influences postnatal B cell and antibody responses in offspring, and that modulation of in utero immune programming may influence immune-modulated diseases later in life.
- Subjects :
- Physiology
animal diseases
Reproductive health and childbirth
Antigen-Antibody Complex
030204 cardiovascular system & hematology
Cardiorespiratory Medicine and Haematology
Inbred C57BL
Cardiovascular
Mice
Maternally-Acquired
0302 clinical medicine
prevention
Immunologic
Pregnancy
2.1 Biological and endogenous factors
Aetiology
Pediatric
Mice, Knockout
0303 health sciences
B-Lymphocytes
biology
adaptive immunity
Acquired immune system
3. Good health
Lipoproteins, LDL
lipids (amino acids, peptides, and proteins)
Female
Rabbits
Antibody
Cardiology and Cardiovascular Medicine
medicine.medical_specialty
Offspring
Knockout
Lipoproteins
Pregnancy Complications, Cardiovascular
Hypercholesterolemia
Clinical Sciences
Mothers
chemical and pharmacologic phenomena
immunization
LDL
Vaccine Related
03 medical and health sciences
Immune system
Antigen
Adjuvants, Immunologic
Immunity
developmental programming
Internal medicine
medicine
Animals
Adjuvants
030304 developmental biology
in utero programming
arteriosclerosis
biochemical phenomena, metabolism, and nutrition
medicine.disease
Atherosclerosis
Mice, Inbred C57BL
Pregnancy Complications
Endocrinology
Good Health and Well Being
Immunization
Immunoglobulin M
Cardiovascular System & Hematology
oxidized LDL
Immunoglobulin G
Immunology
Antibody Formation
Hemocyanins
biology.protein
bacteria
Digestive Diseases
Immunity, Maternally-Acquired
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Circulation research, vol 99, iss 7, Circ Res
- Accession number :
- edsair.doi.dedup.....a3137df58f0cec8dca384a4e9b88ca8e