# MONONUCLEAR PHAGOCYTE FUNCTION IN IMMUNOLOGIC DISEASES

> **NIH NIH R01** · HOSPITAL FOR SPECIAL SURGERY · 1988 · $167,019

## Abstract

Disease-free Caucasians with a haplotype containing the HLA
Class II alloantigens DR2 and DR3, -- the same Class II
alloantigens which are associated with systemic lupus
erythematosus (SLE), -- are more likely to have impaired Fc-
mediated mononuclear phagocyte system clearance than
individuals without these alloantigens.  This same difference is
reflected in the specific impairment of Fc receptor-mediated
phagocytosis by blood monocytes in the same groups.  We
hypothesize that different Fc receptor forms and allelic variants,
which have important functional consequences for the host,
underlie these findings.  Accordingly, the specific aims of this
proposal are:
1. to define the different biochemical forms of Fc-
 gamma receptor and establish the presence or absence
 of a comma polypeptide core;
2. to define the different epitopes on these FcRs by
 monoclonal and polyclonal antibodies;
3. in populations defined by DR type and intrinsic
 phagocytic capacity as we have described, to define
 the expression of different receptors and/or allelic
 forms using a) receptor isolation and analytic
 isoelectric focusing and b) fluorescent analysis with
 monoclonal anti-receptor antibodies;
4. using receptor-specific reagents, to define the
 consequences of ligation specific different FcR forms
 in terms of a) transmembrane signalling events (e.g.,
 intracellular calcium measured by Indo I) and b)
 receptor initiated integrated cell functions (e.g., E-
 ConA phagocytosis in NA1 and NA2 homozygotes).

Phagocytosis by blood monocytes of Fc specific and non-specific
probes is assessed by radiometric incorporation; one- and two-
dimensional SDS-PAGE and Western blotting of affinity-isolated
Fc receptor are used to defined molecular weight, isoelectric
points, lectin-binding and epitope representation.  Electroelution
and HPLC are used for protein purification for sequencing.  Flow
cytometry defines surface epitopes and changes in intracellular
calcium (Indo 1).

These studies will define the mechanism underlying HLA-
associated differences in Fc receptor function and provide a basis
for more guided therapeutic approaches in diseases such as SLE.

## Key facts

- **NIH application ID:** 3156481
- **Project number:** 5R01AR033062-05
- **Recipient organization:** HOSPITAL FOR SPECIAL SURGERY
- **Principal Investigator:** Robert P. Kimberly
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $167,019
- **Award type:** 5
- **Project period:** 1984-09-30 → 1992-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156481

## Citation

> US National Institutes of Health, RePORTER application 3156481, MONONUCLEAR PHAGOCYTE FUNCTION IN IMMUNOLOGIC DISEASES (5R01AR033062-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156481. Licensed CC0.

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