# MECHANISMS OF COMPLEMENT ATTACK ON NUCLEATED CELLS

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1993 · $169,635

## Abstract

The long term objective of our research is to understand the biology of
the terminal complement complex (TCC) which includes C5b-7, C5b-8, and
C5b-9.  C5b-9 mediated nucleated cell killing is governed by a multi-step
process: sequential assembly of TCC in the membrane, elimination of
potentially lytic C5b-9 from the cell surface, and the process of cell
death elicited by C5b-9.  Once TCC is assembled, it is subjected to rapid
elimination from the cell surface.  TCC elimination, vital for cell
survival, is enhanced by increased cytosolic Ca2+, [Ca2+] i, in a protein
kinase C (PKC) -dependent manner when the number of TCC is limiting.
Since elimination of complement channels depends on signals generated by
TCC and TCC is known to be a potent inducer of cell activation, the
effect of C5b-7, C5b-8, and sublytic C5b-9 channels may be of major
biological importance in cells surviving from limited complement attack
in vivo.  Other than Ca2+ influx and increase in [Ca 2+ ]i, little is
known about whether and how TCC generates other signal messengers.
Interestingly, some of the biological activities of C5b-9 can be achieved
by C5b-7 and/or C5b-8 with little or no Ca2+ influx, which suggests that
mediators other than Ca2+ may be involved.  We have been able to
demonstrate that TCC, especially C5b-7, increased the mass levels of
diacylglycerol (DAG) and ceramide, potent second messengers, in a human
JY B cell line and in a murine C2 muscle cell line.  These findings are
potentially significant to understand the pathobiology of affected cells
in autoimmune diseases in which functionally important cells such as
B-cells and muscle cells are targeted by auto-antibodies.

In this proposal, we will examine (1) TCC-induced signal messengers,
specifically DAG and ceramide, and the mechanisms of their generation by
analyzing G protein activation, (2) the regulatory effect of TCC on the
expression of muscle-specific proteins in C2 mytotubes by examining
post-transcriptional stability of mRNAs encoding these proteins, and (3)
the mechanisms of nucleated cell killing mediated by C5b-9 by exploring
the effect of uncontrolled calcium influx on the functional status of
mitochondria.

## Key facts

- **NIH application ID:** 3128947
- **Project number:** 2R01AI019622-11
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** MOON L SHIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $169,635
- **Award type:** 2
- **Project period:** 1983-01-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128947

## Citation

> US National Institutes of Health, RePORTER application 3128947, MECHANISMS OF COMPLEMENT ATTACK ON NUCLEATED CELLS (2R01AI019622-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128947. Licensed CC0.

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