hemolin
Hemolin is an immunoglobulin-like protein exclusively found in Lepidoptera (moths and butterflies). It was first discovered in immune-challenged pupae of Hyalophora cecropia{{cite journal|last=Faye|first=I|author2=Pye, A |author3=Rasmuson, T |author4=Boman, HG |author5= Boman, IA |title=Insect immunity. 11. Simultaneous induction of antibacterial activity and selection synthesis of some hemolymph proteins in diapausing pupae of Hyalophora cecropia and Samia cynthia.|journal=Infection and Immunity|date=December 1975|volume=12|issue=6|pages=1426–38|doi=10.1128/iai.12.6.1426-1438.1975|pmid=812827 |pmc=415452}} and Manduca sexta.{{cite journal|last=Ladendorff|first=NE|author2=Kanost, MR|title=Bacteria-induced protein P4 (hemolin) from Manduca sexta: a member of the immunoglobulin superfamily which can inhibit hemocyte aggregation.|journal=Archives of Insect Biochemistry and Physiology|year=1991|volume=18|issue=4|pages=285–300|pmid=1790333|doi=10.1002/arch.940180410}}
Hemolin has a horseshoe crystal structure{{cite journal|last=Su|first=XD|author2=Gastinel, LN |author3=Vaughn, DE |author4=Faye, I |author5=Poon, P |author6= Bjorkman, PJ |title=Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion.|journal=Science|date=Aug 14, 1998|volume=281|issue=5379|pages=991–5|pmid=9703515|doi=10.1126/science.281.5379.991}} with four domains and resembles the developmental protein neuroglian.
File:Hemolin and neuroglian 3D.png
Hemolin increases 18-fold up to 7 mg/ml following injection of bacteria in H. cecropia. Induction of Hemolin in moths after bacterial injection have been shown in several species including Antheraea pernyi,{{cite journal|last=Li|first=W|author2=Terenius, O |author3=Hirai, M |author4=Nilsson, AS |author5= Faye, I |title=Cloning, expression and phylogenetic analysis of Hemolin, from the Chinese oak silkmoth, Antheraea pernyi.|journal=Developmental and Comparative Immunology|year=2005|volume=29|issue=10|pages=853–64|pmid=15978282|doi=10.1016/j.dci.2005.02.003}} Bombyx mori, Helicoverpa zea,{{cite journal|last=Terenius|first=O|author2=Popham, HJ |author3=Shelby, KS |title=Bacterial, but not baculoviral infections stimulate Hemolin expression in noctuid moths.|journal=Developmental and Comparative Immunology|date=November 2009|volume=33|issue=11|pages=1176–85|pmid=19540262|doi=10.1016/j.dci.2009.06.009|url=https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=36305&content=PDF}} Heliothis virescens,{{cite journal|last=Terenius|first=O|author2=Popham, HJ |author3=Shelby, KS |title=Bacterial, but not baculoviral infections stimulate Hemolin expression in noctuid moths.|journal=Developmental and Comparative Immunology|date=November 2009|volume=33|issue=11|pages=1176–85|pmid=19540262|doi=10.1016/j.dci.2009.06.009|url=https://naldc-legacy.nal.usda.gov/naldc/download.xhtml?id=36305&content=PDF}} Hyphantria cunea,{{cite journal|last=Shin|first=SW|author2=Park, SS |author3=Park, DS |author4=Kim, MG |author5=Kim, SC |author6=Brey, PT |author7= Park, HY |title=Isolation and characterization of immune-related genes from the fall webworm, Hyphantria cunea, using PCR-based differential display and subtractive cloning.|journal=Insect Biochemistry and Molecular Biology|date=November 1998|volume=28|issue=11|pages=827–37|pmid=9818384|doi=10.1016/s0965-1748(98)00077-0}} and Samia cynthia.{{cite journal|last=Bao|first=Y|author2=Yamano, Y |author3=Morishima, I |title=Induction of hemolin gene expression by bacterial cell wall components in eri-silkworm, Samia cynthia ricini.|journal=Comparative Biochemistry and Physiology B|date=January 2007|volume=146|issue=1|pages=147–51|pmid=17126583|doi=10.1016/j.cbpb.2006.10.092}}
Hemolin has also been suggested to participate in the immune response to virus infection{{cite journal|last=Terenius|first=O|title=Hemolin-A lepidopteran anti-viral defense factor?|journal=Developmental and Comparative Immunology|year=2008|volume=32|issue=4|pages=311–6|pmid=17981330|doi=10.1016/j.dci.2007.09.006}} and shown to bind to virus particles.{{cite journal|last=Labropoulou|first=V|author2=Douris, V |author3=Stefanou, D |author4=Magrioti, C |author5=Swevers, L |author6= Iatrou, K |title=Endoparasitoid wasp bracovirus-mediated inhibition of hemolin function and lepidopteran host immunosuppression.|journal=Cellular Microbiology|date=October 2008|volume=10|issue=10|pages=2118–28|pmid=18627380|doi=10.1111/j.1462-5822.2008.01195.x|doi-access=free}} It is expressed in response to dsRNA in a dose-dependent manner.{{cite journal|last=Hirai|first=M|author2=Terenius, O |author3=Li, W |author4= Faye, I |title=Baculovirus and dsRNA induce Hemolin, but no antibacterial activity, in Antheraea pernyi.|journal=Insect Molecular Biology|date=August 2004|volume=13|issue=4|pages=399–405|pmid=15271212|doi=10.1111/j.0962-1075.2004.00497.x|s2cid=46056395}} Galleria melonella responds to caffeine intake by increased Hemolin protein expression.{{Cite journal|last1=Maguire|first1=Ronan|last2=Kunc|first2=Martin|last3=Hyrsl|first3=Pavel|last4=Kavanagh|first4=Kevin|title=Caffeine administration alters the behaviour and development of Galleria mellonella larvae|journal=Neurotoxicology and Teratology|doi=10.1016/j.ntt.2017.10.002|pmid=29024709|volume=64|year=2017|pages=37–44|url=http://mural.maynoothuniversity.ie/11076/1/KK-Caffeine-2017.pdf}}
Hemolin is thought to be a gene duplication of the developmental protein neuroglian,{{cite journal|last=Hughes|first=AL|title=Protein phylogenies provide evidence of a radical discontinuity between arthropod and vertebrate immune systems.|journal=Immunogenetics|date=March 1998|volume=47|issue=4|pages=283–96|pmid=9472064|doi=10.1007/s002510050360|s2cid=36390766 }} but has lost two of the protein domains that neuroglian contains. In the potential function as a developmental protein, Hemolin has been shown to increase close to pupation in Manduca sexta,{{cite journal|last=Yu|first=XQ|author2=Kanost, MR|title=Developmental expression of Manduca sexta hemolin.|journal=Archives of Insect Biochemistry and Physiology|date=Nov 1999|volume=42|issue=3|pages=198–212|pmid=10536048|doi=10.1002/(sici)1520-6327(199911)42:3<198::aid-arch4>3.0.co;2-g}} and is induced during diapause and by 20-Hydroxyecdysone in Lymantria dispar.{{cite journal|last=Lee|first=KY|author2=Horodyski, FM |author3=Valaitis, AP |author4= Denlinger, DL |title=Molecular characterization of the insect immune protein hemolin and its high induction during embryonic diapause in the gypsy moth, Lymantria dispar.|journal=Insect Biochemistry and Molecular Biology|date=November 2002|volume=32|issue=11|pages=1457–67|pmid=12530213|doi=10.1016/s0965-1748(02)00066-8}} RNAi of Hemolin causes malformation in H. cecropia.{{cite journal|last=Bettencourt|first=R.|author2=Terenius, O. |author3=Faye, I. |title=Hemolin gene silencing by ds-RNA injected into Cecropia pupae is lethal to next generation embryos|journal=Insect Molecular Biology|date=June 2002|volume=11|issue=3|pages=267–271|doi=10.1046/j.1365-2583.2002.00334.x|pmid=12000646|doi-access=free}}