# REGULATION OF C-REACTIVE PROTEIN SECRETION

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1990 · $83,777

## Abstract

Recent advances in the understanding of the mechanisms
regulating protein secretion have indicated that secretory
proteins may require differing periods of time to traverse the
secretary pathway.  Studies from our laboratory have shown that
an individual protein, C-reactive protein (CRP), is secreted
markedly faster when its synthesis in the liver is induced during
the acute phase response to inflammation in the rabbit.  This is
the result of a great reduction in the time required for newly-
synthesized CRP to exit from the rough endoplasmic reticulum
(RER) during phase response (APR).  In control animals CRP is
actively retained within the RER and is secreted much less
efficiently.  In preliminary studies we have demonstrated specific
binding of CRP to detergent-permeabilized rough microsomes.
The overall goal of this proposal is to elucidate the mechanism by
which CRP is retained within the RER and how this process is
regulated during the APR.  Specific aims include 1)
characterization of the binding reaction of CRP to microsomes, 2)
localization of the binding site within both microsomes and
hepatocytes, 3) determination of changes in microsomal binding
during the APR, and 4) identification and isolation of the
microsomal binding site for CRP.  Specifically, conditions for
binding will be further optimized with respect to osmotic and
ionic conditions, pH, and detergent-protein ratio.  The relevancy
of this reaction to biologically synthesized CRP will be assessed
by studies of the competition of purified CRP for pulse-labelled
CRP contained in microsomes prepared from cultured
hepatocytes.  The distribution of the binding site within
microsomes and cultured hepatocytes will be determined by
incubating detergent-permeabilized preparations with biotinylated
CRP followed by peroxidase-conjugated Streptavidin.  The
affinity and number of binding sites will be determined by
Scatchard analysis of microsomes prepared from rabbits
manifesting varying degrees of the APR.  Identification of the
binding site will involve affinity chromatography of detergent
extracts on CRP-Sepharose, chemical crosslinking of CRP to
microsomes followed by immunochemical isolation of CRP-linked
complexes, as well as the production of antibodies against the
idiotype of affinity purified anti-CRP immunoglobulin.  The serum
concentration of CRP is markedly elevated in a number of
inflammatory diseases.  CRP itself appears to play a role in the
modulation of the inflammatory response.  Investigation of
mechanisms which control CRP secretion will contribute to our
understanding of the host response to a wide variety of
inflammatory conditions, including many of the rheumatic
diseases.

## Key facts

- **NIH application ID:** 3156792
- **Project number:** 5R01AR034313-06
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** STEPHEN S MACINTYRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $83,777
- **Award type:** 5
- **Project period:** 1984-07-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156792

## Citation

> US National Institutes of Health, RePORTER application 3156792, REGULATION OF C-REACTIVE PROTEIN SECRETION (5R01AR034313-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156792. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*