Normal Biopsy. (of what?). normal. Inflamed Biopsy. inflamed. colon. This session introduces you to an aspect of inflammatory bowel disease (IBD). It explains how hyaluronan may play a role in recruiting inflammatory cells.
Triggers of episodes of IBD are complex and not fully understood. One hallmark of onset is the recruitment of inflammatory cells (red arrow). Some observations: the amount of hyaluronan increases as inflammation increases as do musc. muscosae smc’s.
Smooth muscle cells
from musc. mucosae
Same cells given
followed by adding
Same culture as on
the left except treated
prior to adding monocytes.
In an attempt to understand the possible role of musc. mucosae smc’s
in recruiting inflammatory cells and the role of hyaluronan; smooth muscle cells from
biopsies were grown in culture, “inflamed”, and monocytes were added. The
monocytes stuck, frequently in rows. If the smc cultures were treated
with hyaluronidase prior to adding monocytes, cell attachment was drastically
When smc’s are “inflamed”, they
synthesize long strands
of hyaluronan (green) in this confocal micro-
graph of a cultured
smc. The green on cell surface is also hyaluronan.
When monocytes are added
to “inflamed” cultured smc’s, they preferentially attach to the cables of hyaluronan produced by the muscle cells.
They do not attach to the
hyaluronan patches (white
arrows) on the cell surface.
Does this phenomenon occur
in the actual inflammatory
in the lamina
propria with inter-
cables in active
Low power of
in the lamina
propria in a net of
Step 1. Inflammatory cytokines recruit mononuclear cells and “inflame” smc’s that respond by synthesizing hyaluronan cables (cable formation is more complicated than depicted here and involves some hyaluronan binding molecules not mentioned.)
Step 2. CD44 receptors on mononuclear cells attach to hyaluronan.
Step 3. L-selectin on mononculear cells binds to versican (that is made by smc’s ) which, in turn, is bound to hyaluronan.
Both CD44 and versican are needed to firmly bind mononuclear cells.
This presentation is a very liberal
interpretation of the work by:
Dr. Vincent C. Hascall
Connective Biology Section
Carol de la Motte
Dr. Scott Strong