# DEVELOPMENTAL LUNG PHOSPHOLIPID METABOLISM

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 1994 · $190,874

## Abstract

There are 2 primary focuses of the research in this proposal:  1, to study
the secretion and clearance kinetics of the surfactant proteins SP-A, SP-B,
and SP-C in the preterm in the presence and in the absence of surfactant
treatments, and 2, to investigate the causes and mediators of the pulmonary
edema characteristic of the preterm lung that can secondarily interfere
with surfactant function.  All experiments will be performed in ventilated
preterm lambs with or without surfactant treatments, or in term newborn
lambs. To evaluate surfactant protein secretion kinetics and the
relationships between the proteins and saturated phosphatidylcholine (Sat
PC) we will study preterm and term lambs after the airway instillation of
35S-methionine and 3H-palmitic acid.  We will then prepare 35S surfactant
protein and 3H phospholipid labeled natural sheep surfactant and give trace
or treatment doses to the preterm.  The airspace clearance and lung tissue
localization will be measured versus time to establish the fate of the
proteins and the time relationships with Sat PC.  Since surfactant used
clinically are organic solvent extracts of natural surfactants that lack
SP-A, we will test the effects of such a surfactant prepared from natural
sheep surfactant on endogenous surfactant metabolism using a model with
different lungs of the same animal treated with either natural or organic
solvent extracted surfactant.  Morphometry will be used to characterize the
impact of surfactant treatments on the preterm lung, with the focus being
primarily on changes in the type II cell that may reflect surfactant
phospholipid recycling in the preterm surfactant treated lung.  Other
experiments will explore our concept that phospholipid synthetic rates are
not the major variable in lung maturation - rather the secretory potential
relative to synthetic rate seems to be the critical variable.  We will
correlate biochemical and morphometric date to make this point.  Finally,
the protein leaks that occur immediately following delivery and ventilation
of the preterm seem to be caused by circulating mediators, based on our
preliminary data.  We plan to identify these mediators, concentrating
initially on platelet activating factor and the arachidonic acid cascade.
We will then characterize the maladaptive response of the preterm lung.
The result from these experiments will provide information directly
relevant for both the design of surfactants for the treatment of
respiratory distress syndrome and for interpreting clinical responses in
terms of surfactant component mass action.  The studies of protein leaks
may identify treatment approaches for the tiny preterm.

## Key facts

- **NIH application ID:** 2196927
- **Project number:** 5R01HD012714-16
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **SAM.gov UEI:** LTJVF4QSFCP9
- **Principal Investigator:** Michael Glenn Ross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $190,874
- **Award type:** 5
- **Project period:** 1979-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196927

## Citation

> US National Institutes of Health, RePORTER application 2196927, DEVELOPMENTAL LUNG PHOSPHOLIPID METABOLISM (5R01HD012714-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196927. Licensed CC0.

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