# BIOCHEMICAL BASIS OF PHAGOCYTOSIS

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 1988 · $167,771

## Abstract

The program aims to examine the significance of changes that
phagocytic leukocytes undergo when they ingest bacteria, with
respect to the role those changes play in protecting the host.  The
leukocytes may be stimulated by solid particles, or by some more
soluble substances, to produce and release compounds of both
leukocytic and bacterial origin.  These phenomena are relevant to
maintenance of health, because they provide a bulwark against
infection.  On the other hand, some biochemical sequelae of this
stimulation may injure host cells.   Generation and release of
activated oxygen species is a key phenomenon in these contexts.
Studies of the nature of the enzymes involved, of the "trigger"
mechanism for stimulation of phagocytic cells, and of
morphological changes the leukocytes undergo, have been made,
and will be extended.  The focus will be on  the effects of some to
the very molecules that phagocytes release from bacteria upon
the phagocytic leukocytes themselves.  Some other cells may also
be affected.  For example, monomeric breakdown-products of
bacterial cells walls are well known as immuno-adjuvants and
pyrogens, and have now been found to be somnogens.  Binding
sites (receptors?) for these substances have been found on
macrophages, and, in preliminary work, on glial but not neuronal
cells.  These binding sites will be characterized,  their variation
followed as a function of the condition of the animal, and
physiological effects ascribed to the ligand related to occupancy
of the cellular binding sites.  Radioactive (125I) muramyl ligands
have been made and the conditions for binding studies are
established.  Attempts to isolate the receptor (binding) proteins
will employ methods that include affinity columns with
immobilized peptidoglycans.  Muramyl peptides (exogenous
substances) and an endogenous substance (serotonin) mimic each
other "pharmacologically."  Thus, muramyl peptides induce slow-
wave sleep in which serotonin has been implicated.  Indications
are that the latter substance "activates" macrophages, e.g., by
conditioning them to release activated oxygen species upon later
stimulation - a function of muramyl peptides.  Work will examine
aspects of the synergism between stimuli and ionophores (for
Ca++) and possible physiologically significant synergistic
situations.  Further, environmental (bodily) components may
affect the lipid matrix of the phagocytic cell - membrane,
triggering release of active oxygen species as shown in vitro.
Both these matters could be of importance in vivo in bacterial
infections, as may be the implications of the somnogenic activity
of muramyl peptides.

## Key facts

- **NIH application ID:** 3124128
- **Project number:** 5R01AI003260-29
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **SAM.gov UEI:** JDLVAVGYJQ21
- **Principal Investigator:** MANFRED L KARNOVSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $167,771
- **Award type:** 5
- **Project period:** 1978-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124128

## Citation

> US National Institutes of Health, RePORTER application 3124128, BIOCHEMICAL BASIS OF PHAGOCYTOSIS (5R01AI003260-29). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3124128. Licensed CC0.

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