Abstract
The cytokine receptor-like factor 3 (CRLF3) is an evolutionary conserved class 1 cytokine receptor present in all major eumetazoan groups. Endogenous CRLF3 ligands have not been identified and the physiological responses mediated by mammalian CRLF3 are poorly characterized. Insect CRLF3 is activated by erythropoietin (Epo) and several related molecules that protect mammalian neurons from stress-induced apoptosis. However, insects neither express Epo nor “classical” Epo receptor. Cell-protective effects of insect hemolymph have been described for several species. In this study, we explored the possibility that the endogenous CRLF3 ligand is contained in locust hemolymph. PCR analyses confirmed expression of crfl3-transcripts in neurons and hemocytes of Locusta migratoria and Tribolium castaneum. Survival of locust hemocytes in primary cultures was significantly increased by supplementation of culture medium with locust hemolymph serum. Locust primary neuron cultures were also protected by locust hemolymph, though preceding exposure to fetal bovine serum changed the hemolymph dose-dependency of neuroprotection. Direct comparison of 10% hemolymph serum with recombinant human Epo in its optimal neuroprotective concentration revealed equivalent anti-apoptotic effects on hypoxia-exposed locust neurons. The same concentration of locust hemolymph serum also protected hypoxia-exposed T. castaneum neurons. This indicates that the neuroprotective factor in locust hemolymph is sufficiently conserved in insects to allow activation of neuroprotective receptors in different species. Locust hemolymph-induced neuroprotection in both L. migratoria and T. castaneum was abolished after RNAi-mediated suppression of crlf3-expression. In summary, we report the presence of a conserved endogenous cytokine in locust hemolymph that activates CRLF3 and connected anti-apoptotic processes in hemocytes and neurons. Identification and characterization of the CRLF3 ligand will promote knowledge about cytokine evolution and may unravel cell-protective agents with potential clinical application.
Highlights
Insect hemolymph contains multiple cell types, suspended in a protein-rich liquid plasma, that circulates through the body cavity of the organism
We investigated effects on hemocytes, the cells that naturally are directly exposed to signals that circulate within the hemolymph serum
cytokine receptor-like factor 3 (CRLF3) has previously been identified as a neuroprotective receptor in L. migratoria and T. castaneum
Summary
Insect hemolymph contains multiple cell types, suspended in a protein-rich liquid plasma, that circulates through the body cavity of the organism (reviewed by Douglas and Siva-Jothy, 2013; Hillyer and Pass, 2020). In contrast to the mammalian acquired immunity involving specific antibodies and memory cells, insects rely on innate immune functions to neutralize various kinds of pathogens (Lavine and Strand, 2002; Siva-Jothy et al, 2005; Strand, 2008). Hemolymph proteins involved in immune functions and adaptation to environmental challenges are synthesized and released into the circulation by the fat body, midgut, endocrine glands such as corpora allata or the corpora cardiaca, neurosecretory cells, hemocytes, and other organs (Arrese and Soulages, 2010; Oda et al, 2010; Roma et al, 2010; Hoshizaki, 2013; Kodrík et al, 2015)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
