Zuckerman, Steven H., Ph.D.
Macrophage Biology
Eli Lilly and Company
The macrophage represents an immunologic cell type which
plays a central role in homeostasis and host defense and yet
with aberrant regulation, can also contribute to morbidity
and mortality in both inflammatory and autoimmune diseases.
To investigate this cell type we have considered the regulation
of cytokine synthesis, primarily TNF and IL-1, by inflammatory
mediators and the mechanisms involved in macrophage desensitization
to bacterial endotoxin in primary macrophage cultures derived
from diverse anatomic sites. We have characterized DNA binding
proteins and both transcriptional and post-transcriptional
pathways involved in this regulation. We have also evaluated
changes in the expression of macrophage surface antigens and
receptors and have investigated the secretion of proteins
involved in cholesterol transport, a role critical for reversing
the progression of atherosclerotic lesions. The combination
of cytokine ELISAs, reverse transcriptase PCR, immunoprecipitations
and Western blot analysis as well as dual label flow cytometry
have enabled us to further understand the changes associated
with macrophage activation. While most of our studies focus
on peritoneal macrophages from control, BALB/c mice, comparative
studies with macrophages from autoimmune mice displaying a
Lupus like disease and cholesterol laden macrophages from
mice having pathologically abnormal cholesterol levels continues
to contribute to our understanding of the role of the macrophage
in host defense and in disease.
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Department of Biology