Zebrafish mast cells possess an FcɛRI-like receptor and participate in innate and adaptive immune responses.
We previously identified a zebrafish mast cell (MC) lineage and now aim to determine if these cells function analogously in innate and adaptive immunity like their mammalian counterparts. Intraperitoneal (IP) injection of compound 48/80 or live Aeromonas salmonicida resulted in significant MC degranulation evident histologically and by increased plasma tryptase compared with saline-injected controls (p=0.0006, 0.005, respectively). Pre-treatment with ketotifen abrogated these responses (p=0.0004, 0.005, respectively). Cross-reactivity was observed in zebrafish to anti-human high-affinity IgE receptor gamma (FcɛRIγ) and IgE heavy chain-directed antibodies. Whole mount in situ hybridization on 7-day embryos demonstrated co-localization of cpa5, a MC-specific marker, with myd88, a toll-like receptor adaptor, and zebrafish FcɛRI subunit homologs. Zebrafish injected IP with matched dinitrophenyl-sensitized mouse (anti-DNP) IgE and DNP-BSA or trinitrophenyl-sensitized mouse (anti-TNP) IgE and TNP-BSA demonstrated increased plasma tryptase compared with mismatched controls (p=0.03, 0.010, respectively). These results confirm functional conservation and validate the zebrafish model as an in vivo screening tool for novel MC modulating agents.
Da'as
Sahar
S
IWK Health Centre, Dalhousie University, PO Box 9700, 5850/5980 University Avenue, Halifax, NS B3K 6R8, Canada.
Teh
Evelyn M
EM
Dobson
J Tristan
JT
Nasrallah
Gheyath K
GK
McBride
Eileen R
ER
Wang
Hao
H
Neuberg
Donna S
DS
Marshall
Jean S
JS
Lin
Tong-Jun
TJ
Berman
Jason N
JN
D056704:Adaptive Immunity; D000595:Amino Acid Sequence; D000818:Animals; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007113:Immunity, Innate; D007665:Ketotifen / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D017455:Receptors, IgE / Q000235:genetics* / Q000276:immunology*; D016415:Sequence Alignment; D015027:Zebrafish / Q000145:classification / Q000276:immunology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D017455:Receptors, IgE; D003189:p-Methoxy-N-methylphenethylamine; D007665:Ketotifen