# ACTIVATION OF PROTEINASES BY PEMPHIGUS ANTIBODY

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1988 · $232,149

## Abstract

Plasminogen activator is a proteinase found in a number of different cells
and tissues which activates plasminogen to plasmin.  In human epidermal
cells the anticell surface pemphigus antibody increases plasminogen
activator (PA) activity.  PA activity appears to be related to:  induction
of synthesis of enzyme protein by a variety of stimuli, activation of
precursor zymogen, compartmentalization of enzyme in the cell and the
extra-cellular space, and interaction with cellular and serum proteinase
inhibitors.  PA may induce biological effects directly or through its
activation of plasminogen to the broad specificity proteinase plamsin.  The
aims of this proposal are directed towards an understanding of plasminogen
activator in epidermal biology with special focus upon its modulation by
the anti-cell surface pemphigus antibody.  We will:  (1) define the
biochemistry of PA synthesis in human epidermis using enzymological and
immunochemical means; (2) study the localization of PA within human
epidermal cells in culture and in tissue using biochemical, immunochemical
and immunocytological methods; (3) purify the epidermal proteinase
inhibitors; (4) explore the effects of a variety of biological factors on
PA synthesis and secretion of human epidermal cells in culture; (5)
determine levels of messenger RNA for plasminogen activator; (6) determine
the mechanism for enhancement of PA synthesis and secretion in pemphigus;
(7) study early events in pemphigus activation, at the membrane, including
studies of arachidonic acid metabolism and cyclic nucleotide metabolism;
(8) evaluate a variety of monoclonal antibodies for their ability to induce
PA synthesis; (9) evaluate the role of PA and plasmin in acantholysis in
vivo, in humans and experimental animals; (10) define the effects of
immunomodulators, such as lymphokines and light upon PA synthesis and
secretion; (11) determine whether abnormalities of PA occur in other
genetic acantholytic diseases.

## Key facts

- **NIH application ID:** 3156180
- **Project number:** 5R01AR032069-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** GERALD S. LAZARUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $232,149
- **Award type:** 5
- **Project period:** 1982-08-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156180

## Citation

> US National Institutes of Health, RePORTER application 3156180, ACTIVATION OF PROTEINASES BY PEMPHIGUS ANTIBODY (5R01AR032069-07). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156180. Licensed CC0.

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