LAL Non-Endotoxin Reactivity - Surprisingly Non-specific

Abstract

Nature abounds in producing a variety of molecules. This is a good thing, however, in endotoxin detection a requirement for an analytical assay is “specificity”. Unfortunately, LAL has been found to be increasingly non-specific since the inception of its use in lieu of the rabbit pyrogen test. Fortunately, there are viable workarounds in terms of using Limulus-based testing where non-endotoxin reactive substance false-reactivity is problematic. In analytical testing, just as in metazoan immune detection of potential microbial invaders, context is everything. The horseshoe crab from which LAL is derived swims and crawls on a beach interface that teems with Gram Negative bacteria (GNB), estimated by some at over 10⁶ CFUs/mL. In this context, the extreme sensitivity of Limulus hemolymph to GNB evolved over the eons. However, it also evolved to detect many other substances relevant to the sea/shore paradigm. This includes especially glucans from fungi and algae/lichens (also widely found in terrestrial plants) and also cellulose and mannans as microbial sugars.