The Involvement of Complement Receptor Type 3 (CR3;CDll b/CD18) in Neutrophil Adhesion and Opsonin-Independent Phagocytosis
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Authors
Zarewych, Dianna
Issue Date
1996
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
𝛽2 integrins, such as complement receptor type 3 (CR3;CDll b/CDI8), relay
proinflammatory signals from GPI-linked proteins through exodomains to the
cytoskeleton. Recent studies suggested that CR3 interacts physically and functionally
with glycosylphosphatidylinositol (GPI)-linked membrane proteins. Our studies tested
the hypothesis that CR3 can physically associate with CD 14, a GPI-linked membrane
protein, under certain conditions. The CD 14 molecule is a membrane binding site for
lipopolysaccharide (LPS), an endotoxin. Although CD14 lacks transmembrane and
cytoplasmic sequences, it activates CR3-mediated neutrophil adhesion and cytokine
release. Using resonance energy transfer microscopy, we show that LPS in the presence of serum or LPS binding protein (LBP) triggers formation of CD 14-CR3 complexes. The kinetic studies in this report show that CD 14-CR3 complexes dissociate as neutrophils attach to substrates. We speculate that LPS-charged CD14 enhances CR3-mediated adhesion by directly binding to CR3. Additionally, we have tested the role of lectin-like interactions, with particluar emphasis on CR3, in phagocytosis of non-opsonized E. coli by neutrophils. A recent study revealed specific saccharides which inhibit lectin-like sites on CR3. In addition to this, another study, focusing on GPI-linked membranes, recognized CD 14 to be involved in the uptake of nonopsonized gram-negative bacteria. With reference to these two studies, we speculated that an interaction may take place between a GPI-linked receptor and CR3, in which a lectin-like interaction may be necessary for signaling transmission to be successful. We show the saccharides N-acetyl-D- glucosamine (NADG) and 𝛽-Glucan have the ability to affect phagocytosis,
dramatically reducing internalization of non-opsonized gram-negative bacteria. Data
presented in this report suggests that NADG and 𝛽-Glucan most likely bind to the lectin-like site on CR3 and block the activation signal for phagocytosis, which could possibly be initiated by a GPI-anchored protein.
Description
viii, 37 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.