The Invertebrate Defence Molecule Coelomic Cytolytic Factor, a Functional Analog of the Cytokine Tumour Necrosis Factor‐α, Interacts with Mammalian Cells through its Lectin‐Like Domain

Abstract

Coelomic cytolytic factor (CCF) is a 42 kDa invertebrate pattern recognition molecule isolated from the coelomic fluid of the earthworm Eisenia foetida (Oligochaeta, Annelida). CCF displays a number of similarities with the mammalian cytokine tumour necrosis factor‐α (TNF‐α) as a result of a shared N,N′‐diacetylchitobiose lectin‐like domain. However, these similarities are solely functional and are not based on any (DNA or amino acid) sequence homology, thus suggesting a form of convergent evolution. In particular, the lectin‐like domain of TNF‐α has been shown to induce membrane depolarization in various mammalian cell types, through interactions with endogenous amiloride‐sensitive ion channels. This nonreceptor‐mediated activity of TNF‐α has been reported to be involved in the resorption of oedema. Likewise, the lectin‐like domain of CCF also induces membrane depolarization in mammalian cells. Here, we show that CCF appears to be able to induce oedema resorption in an alveolar epithelial cell line through its lectin‐like domain. This lectin‐like domain of CCF interacts (directly or indirectly) with endogenous sodium and/or chloride channels, and not potassium channels, on mammalian cells. Additionally, we suggest that the JNK/SAPK and Erk1/2 pathways are involved in CCF‐induced macrophage activation. These results further establish the functional analogy between an invertebrate pattern recognition molecule and a mammalian cytokine and, from a more applied point of view, suggest the possibility of utilizing CCF in the treatment of oedema.