We have established a mouse model for examining several basic questions about the role of acute phase reactants (APR) in nonspecific host resistance. The model is based on serum amyloid P-component (SAP), the major acute phase reactant of mice, which is a molecular homologue of C-reactive protein (CRP), the prototype APR in humans. Methods for purification and quantitation (ELISA) of mouse SAP have been developed. The mouse strain variation in the endogenous level of SAP and the extent of the response have allowed us to map the gene controlling SAP levels to the distal end of chromosome 1 with close linkage to the Ly-9, Mls, and H-25 loci. A congenic strain for the BALB/c H-25 locus, which is on the low SAP background of C57BL/6ByJ mice is being used to study the role of SAP in resistance to microbial and viral infections. The congenic strain is more susceptible to Listeria infections than the parental strain. The in vitro induction and synthesis of SAP by mouse hepatocytes is driven primarily by IL-1 but is enhanced by two other monokines of 30 kilodalton and 80 kilodalton. Hepatocyte recruitment into new SAP synthesis is observed in cultures containing both hepatocytes and macrophages (and/or IL-1) when measured by a single-cell assay detecting SAP-secreting hepatocytes. The non-IL-1 monokines recruit hepatocytes. Purified mouse SAP is a potent inducer of additional IL-1 production by elicited macrophages and therefore has the potential to amplify the inflammatory response. One consequence of this activity is that SAP enhances IgG production in vitro in response to T-dependent antigens. Thus, APRs that arise during an inflammatory response may not only contribute to nonspecific host resistance but also may enhance subsequent specific immunity. (HF)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA030015-09
Application #
3168974
Study Section
Immunobiology Study Section (IMB)
Project Start
1980-08-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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