Control of the Hyaluronidase Activity Towards Hyaluronan by Formation of Electrostatic Complexes: Fundamental and Application Relevance - Natural Polymers, Biopolymers, Biomaterials, and Their Composites, Blends, and IPNs - page 124

Chapter 12
Control of the hyaluronidase activity towards
hyaluronan by Formation of electrostatic
Complexes: Fundamental and application
relevance
Brigitte Deschrevel
iNtroduCtioN
Hyaluronan (HA) is a glycosaminoglycan (GAG) widely distributed in vertebrate tis-
sues. Due to its unique biophysicochemical properties, it is involved in many bio-
logical processes under both normal and pathological conditions. In addition, HA and
its derivatives are used in various medical and aesthetic applications. However, the
biophysicochemical properties and biological functions of HA strongly depend on its
chain size. By catalyzing HA hydrolysis hyaluronidases (HAases) play an important
role in the control of the HA chain size. Our study of the kinetics of the HA hydrolysis
catalyzed by HAase led us to the conclusion that two phenomena should be taken into
account to properly describe the behavior of the hyaluronan/hyaluronidase system: (i)
formation of catalytic complexes which leads to HA hydrolysis and (ii) formation of
electrostatic hyaluronan hyaluronidase complexes in which hyaluronidase is catalyti-
cally inactive. As a consequence, the hyaluronidase activity can be strongly modulated
by formation of electrostatic complexes involving either HA and/or hyaluronidase.
The present report shows that this knowledge of the behavior of the hyaluronan/hyal-
uronidase system is important with respect to the detection, quantification, character-
ization, and use of hyaluronidase. It also strongly suggests that this behavior could be
of importance under in vivo conditions, since, for example, it was shown that, accord-
ing to its concentration, a hyaladherin (protein able to specifically bind HA) is able to
either enhance or suppress the activity of a tumoral hyaluronidase.
The HA, also known as hyaluronic acid is a polysaccharide which belongs to the
GAG family. It is widely distributed in vertebrate tissues and fluids and is the most
abundant GAG in mammalian tissues. In human body, HA concentration varies over
a wide range; for example, it ranges from 1,420 to 3,600 mg l -1 in synovial fluids, it
is around 200 mg l -1 in dermis and between 0.02 and 0.04 mg l -1 in blood serum and
plasma (Chichibu et al., 1989; Engstrom-Laurent et al., 1985; Laurent and Fraser,
1986). In connective tissues, HA is one of the main components of the extra-cellular
matrix (ECM). The HA is composed by the repetition of D-glucuronic acid-b(1,3)-
N-acetyl-D-glucosamine disaccharide units linked through b(1,4) glycosidic linkages
(Figure 1). It is unbranched, not sulfated nor modified in any other way throughout its
length, all of which makes it the simplest of the GAGs. Under normal physiological