Biomedical Engineering Reference
In-Depth Information
proteolytically active equivalent Sar s 3 has no effect on complement but plays a
pivotal role in digesting filaggrin, a dominant protein forming the functional
barrier of the stratum corneum.
60
SMIPPs may be only one of several strategies that the mite has invented to
overcome host defenses. We have preliminary evidence of at least two other
multigene families of scabies mite molecules inhibiting complement. It is also
likely that other host systems such as coagulation or epidermal desquamation
may be inhibited by scabies mite proteins. The inhibition of host defenses
concentrated in the microenvironment of the scabies mite burrows may well be
utilized to the advantage of scabies-associated bacterial pathogens such as GAS.
We are currently refining evidence that supports this hypothesis and investi-
gating the SMIPP-S binding mechanism to complement factors, with the aim to
develop complement-inhibiting peptides. This may possibly be the way forward
to a new generation of scabies control agents. Moreover, the discovery of mite-
derived complement inhibitors may have a much wider utility elsewhere. As an
integral part of the host innate and adaptive immune systems, the pro-inflam-
matory nature of complement lies at the basis of a number of different diseases,
including ischaemia-reperfusion injury following myocardial infarction, neu-
rodegenerative diseases, and a large number of other conditions. Hence, there is
the potential for extrapolation into numerous areas of human health.
4.4.2 Complement-Subversion Strategies in Other Parasitic
Organisms
Parasitic worms, commonly referred to as blood flukes, are the causative agents
of schistosomiasis. There are an estimated 200 million people worldwide
infected by the three main human-infecting species Schistosoma mansoni,
Schistosoma japonicum, and Schistosoma haematobium.
61
Schistosomes have a
complex lifecycle within an intermediate host (freshwater snails) and the defi-
nitive host (humans). Within the human host, the worms reside in the mesen-
teric and portal blood vessels where they employ several strategies designed to
evade complement on multiple levels.
62
Paramyosin was first characterized in
schistosomes in 1986 as a 97 kDa immunogenic molecule recognized by anti-
bodies raised in mice vaccinated against Schistosoma mansoni.
63
Termed Sm97
at the time, Lanar et al. later demonstrated that Sm97 was paramyosin, a
known muscle protein of invertebrates. Comparative studies with other para-
myosins led Lanar et al. to conclude that schistosomal paramyosin played a
specific role in muscle contraction.
64
Localization of paramyosin with Sm97-
specific antibodies by immunofluorescence to the tegument muscle region
below the parasite skin surface reinforced this conclusion.
63
When paramyosin
was shown to be a potential vaccine candidate, Pearce et al. suggested that
paramyosin must be either expressed on the surface at some time or excreted in
order for the immune system to recognize the muscle protein.
65
The localization
of a non-filamentous membrane bound form of paramyosin to the outer layer
of the tegument,
66
and later on the parasite surface,
67
confirmed this hypoth-
esis. Subsequent functional studies of paramyosin in Schistosoma mansoni,