PMID- 29641231 OWN - NLM STAT- MEDLINE DCOM- 20190715 LR - 20240312 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 315 IP - 2 DP - 2018 Aug 1 TI - A role for the CXCR4-CXCL12 axis in the little skate, Leucoraja erinacea. PG - R218-R229 LID - 10.1152/ajpregu.00322.2017 [doi] AB - The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate ligand C-X-C motif chemokine ligand 12 (CXCL12) plays a critical role in regulating hematopoietic stem cell activation and subsequent cellular mobilization. Extensive studies of these genes have been conducted in mammals, but much less is known about the expression and function of CXCR4 and CXCL12 in non-mammalian vertebrates. In the present study, we identify simultaneous expression of CXCR4 and CXCL12 orthologs in the epigonal organ (the primary hematopoietic tissue) of the little skate, Leucoraja erinacea. Genetic and phylogenetic analyses were functionally supported by significant mobilization of leukocytes following administration of Plerixafor, a CXCR4 antagonist and clinically important drug. Our results provide evidence that, as in humans, Plerixafor disrupts CXCR4/CXCL12 binding in the little skate, facilitating release of leukocytes into the bloodstream. Our study illustrates the value of the little skate as a model organism, particularly in studies of hematopoiesis and potentially for preclinical research on hematological and vascular disorders. FAU - Hersh, Taylor A AU - Hersh TA AUID- ORCID: 0000-0002-7891-596X AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. FAU - Dimond, Alexandria L AU - Dimond AL AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. AD - School of Arts and Sciences, Endicott College , Beverly, Massachusetts. FAU - Ruth, Brittany A AU - Ruth BA AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. AD - School of Arts and Sciences, Endicott College , Beverly, Massachusetts. FAU - Lupica, Noah V AU - Lupica NV AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. FAU - Bruce, Jacob C AU - Bruce JC AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. FAU - Kelley, John M AU - Kelley JM AD - School of Arts and Sciences, Endicott College , Beverly, Massachusetts. AD - Beth Israel Deaconess Medical Center, Program in Placebo Studies, Harvard Medical School , Boston, Massachusetts. FAU - King, Benjamin L AU - King BL AD - Department of Molecular and Biomedical Sciences, University of Maine , Orono, Maine. FAU - Lutton, Bram V AU - Lutton BV AD - Mount Desert Island Biological Laboratory , Bar Harbor, Maine. AD - School of Arts and Sciences, Endicott College , Beverly, Massachusetts. LA - eng GR - P20 GM103423/GM/NIGMS NIH HHS/United States GR - P20 GM104318/GM/NIGMS NIH HHS/United States GR - R25 ES016254/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20180411 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Benzylamines) RN - 0 (Chemokine CXCL12) RN - 0 (Cyclams) RN - 0 (Fish Proteins) RN - 0 (Heterocyclic Compounds) RN - 0 (Receptors, CXCR4) RN - S915P5499N (plerixafor) SB - IM MH - Animals MH - Benzylamines MH - Chemokine CXCL12/genetics/*metabolism MH - Cyclams MH - Fish Proteins/genetics/*metabolism MH - Gene Expression Regulation MH - Hematopoietic Stem Cells/drug effects/*metabolism MH - Heterocyclic Compounds/pharmacology MH - Leukocytes/drug effects/*metabolism MH - *Leukopoiesis/drug effects/genetics MH - Phylogeny MH - Receptors, CXCR4/antagonists & inhibitors/genetics/*metabolism MH - Signal Transduction MH - Skates, Fish/genetics/*metabolism MH - Transcriptome PMC - PMC6139610 OTO - NOTNLM OT - C-X-C chemokine ligand 12 OT - C-X-C chemokine receptor type 4 OT - Plerixafor/AMD3100 OT - elasmobranch OT - mobilization EDAT- 2018/04/12 06:00 MHDA- 2019/07/16 06:00 PMCR- 2019/08/01 CRDT- 2018/04/12 06:00 PHST- 2018/04/12 06:00 [pubmed] PHST- 2019/07/16 06:00 [medline] PHST- 2018/04/12 06:00 [entrez] PHST- 2019/08/01 00:00 [pmc-release] AID - R-00322-2017 [pii] AID - 10.1152/ajpregu.00322.2017 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2018 Aug 1;315(2):R218-R229. doi: 10.1152/ajpregu.00322.2017. Epub 2018 Apr 11.