Hersh Taylor A, Dimond Alexandria L, Ruth Brittany A, Lupica Noah V, Bruce Jacob C, Kelley John M, King Benjamin L, Lutton Bram V
Mount Desert Island Biological Laboratory , Bar Harbor, Maine.
School of Arts and Sciences, Endicott College , Beverly, Massachusetts.
Am J Physiol Regul Integr Comp Physiol. 2018 Aug 1;315(2):R218-R229. doi: 10.1152/ajpregu.00322.2017. Epub 2018 Apr 11.
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.
C-X-C趋化因子受体4（CXCR4）与其同源配体C-X-C基序趋化因子配体12（CXCL12）之间的相互作用在调节造血干细胞激活及随后的细胞动员中起着关键作用。在哺乳动物中已经对这些基因进行了广泛研究，但对于非哺乳动物脊椎动物中CXCR4和CXCL12的表达及功能了解较少。在本研究中，我们鉴定出小斑鳐（Leucoraja erinacea）的性腺器官（主要造血组织）中同时表达CXCR4和CXCL12的直系同源物。给予普乐沙福（一种CXCR4拮抗剂和临床上重要的药物）后白细胞显著动员，这在功能上支持了遗传和系统发育分析。我们的结果提供了证据，即与人类一样，普乐沙福破坏了小斑鳐体内CXCR4/CXCL12的结合，促进白细胞释放到血液中。我们的研究说明了小斑鳐作为一种模式生物的价值，特别是在造血研究以及潜在的血液学和血管疾病临床前研究方面。
