# LEISHMANIA DONOVANI ACID PHOSPHATASE

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1989 · $92,575

## Abstract

Leishmania donovani, the causitive agent in Kala-azar, is deficient in most
acid hydrolases, but contains intense acid phosphatase activity that is
localized to the surface of promastigotes grown in culture.  During the
previous grant period we purified this tartrate-resistant phosphatase to
homogeneity, starting from a sodium cholate extract of membranes, and
characterized some of its physical-chemical and kinetic properties.  The
enzyme exhibits protein phosphatase activity at pH 7.0 and dephosphorylates
32p-labeled macrophage membrane proteins.  The phosphatase also reduces
superoxide anion production by phagocytic cells and inhibits their ability
to destroy bacteria.  Our central hypothesis is that the cell surface acid
phosphatase disarms defense mechanisms of host cells by dephosphorylating
key regulatory phosphoproteins of these phagocytic cells.

During the next grant period, we will continue to define the
physical-chemical and kinetic properties of the tartrate-resistant acid
phosphatase.  We will define its composition and partially characterize its
carbohydrate domains.  The inhibitory effects of the polyheterometallate
complexes will be investigated with the ultimate goal being to use these
compounds to investigate the pathophysiological role of the leishmanial
phosphatase.  In terms of substrate specificity, emphasis will be placed on
identifying cell surface phosphoproteins that are substrates for the enzyme.

The other areas of the work plan are directed at characterizing the effects
of the tartrate-resistant phosphatase on a variety of specific phagocytic
cell functions; we will investigate the effect of the enzyme on:
phagocytosis, the plasma membrane potential, the secretion of granule
enzymes and proteins, the production of oxygen-dependent cidal compounds
(e.g., O-2, H2O2, OC1-, C12) and arachidonic acid metabolites, NADPH
oxidase activity, lysosomal pH and lysosomal hydrolase function.  Finally,
we will use antibodies against the phosphatase, as well as the phosphatase
itself, to directly assess the importance of the enzyme in the killing of
promastigotes by macrophages and neutrophils.

The results of this study could provide insight into improved diagnostic
and therapeutic strategies for leishmaniasis.

## Key facts

- **NIH application ID:** 3128339
- **Project number:** 5R01AI018945-08
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** ROBERT H GLEW
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $92,575
- **Award type:** 5
- **Project period:** 1982-05-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128339

## Citation

> US National Institutes of Health, RePORTER application 3128339, LEISHMANIA DONOVANI ACID PHOSPHATASE (5R01AI018945-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128339. Licensed CC0.

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