Project: Research project

Project Details


The specific aim of this proposal is to elucidate the mechanism by which
autacoids that influence cyclic nucleotides (cAMP and cGMP) production
modulate the function of glomerular mesangial cells in culture. Mesangial
cells possess properties similar to other inflammatory cells and are
potentially capable of oxygen radical production and lysosomal enzyme
release. These mediators may inflict auto-injury or injury to neighboring
cells or extracellular structures that maintain the integrity of the
glomerular basement membrane barrier. Experiments will be performed to
quantitate the production of superoxide anion, hydrogen peroxide and
hydroxyl radical in response to soluble surface stimuli e.g. chemotactic
peptides or phorbol esters and particulate stimuli e.g. opsonized zymosan.
In addition the kinetics of the release of two marker lysosomal enzymes
Beta-glucoronidase and Beta-glucosidase will be studied. We will explore the role of the cyclic nucleotides (cAMP and cGMP) as
mediators of the effect of the renal autacoids and neurotransmitters
histamine, isoproterenol, adenosine, prostaglandin E2 and carbamylcholine
on lysosomal enzyme release and oxygen radical production by rat mesangial
cells in culture. We will determine if these hormones increase or decrease
radical production or enzyme release, if these effects parallel their
effects on cyclic nucleotides, and if cyclic nucleotide analogues mimic the
effect of the hormones. Since calcium subserves a critical role in oxygen radical production and
lysosomal enzyme release by inflammatory cells. We will explore the role
of extracellular and intracellular calcium by studying the effect of
calcium channel blockers and agents that antagonize the release of
intracellular calcium, on radical production and enzyme release by
mesangial cells. In addition, we will attempt to measure simultaneous
changes in cytoplasmic calcium concentration using quin 2, a newly
synthesized intracellular fluorescent calcium indicator. These studies will elucidate the kinetics of oxygen radical production and
lysosomal enzyme release and determine the role of calcium in modulating
these processes, in glomerular mesangial cells. Such information will
enhance our understanding of the inter-relationship between inflammatory
mediators and intrinsic glomerular cells.
Effective start/end date12/1/8411/30/87


  • National Institutes of Health


  • Medicine(all)


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