GUINEA-PIG SERUM ERYTHROPOIETIN (EPO) SELECTIVELY STIMULATES GUINEA-PIG ERYTHROID PROGENITORS - HUMAN OR MOUSE ERYTHROID PROGENITORS DO NOTFORM ERYTHROID BURST-FORMING UNIT COLONIES IN RESPONSE TO GUINEA-PIG SERUM EPO

Erythropoietin (EPO) is the primary regulator of mammalian erythropoie sis, providing a proliferative and differentiative signal to the early EPO-responsive erythroid progenitors, burst-forming unit-erythroid (B FU-E) and colony-forming unit-erythroid, as well as to later EPO-respo nsive Erythroid progenitors. EPO is secreted by the kidney in response to hypoxia and anemia. There is an extensive biological crossreactivi ty between human EPO and the EPOs of other mammals. Necas et al, have reported that this crossreactivity may not include the guinea pig (Cav ia porcellus). Because the specificity of the guinea pig's erythropoie tic responses may be of biological significance, we compared guinea pi g hypoxic serum with mouse (m) and human (h) recombinant (r) EPOs for their ability to induce erythroid progenitor proliferation and differe ntiation in semisolid cultures. Guinea pig bone marrow mononuclear cel ls (BMMCs) formed BFU-E colonies in response to guinea pig hypoxic ser um, rhEPO, or rmEPO in a dose-dependent fashion, Neither human nor mou se BMMCs responded to guinea pig hypoxic serum; however, guinea pig hy poxic serum exerted no inhibitory effect on human or mouse in vitro er ythroid differentiation in the presence of rhEPO or rmEPO. The intensi ty of the EPO band on Western blotting analysis of guinea pig hypoxic serum was significantly greater than in nonhypoxic serum. This suggest s that guinea pig erythropoiesis is mediated by EPO and stimulated by hypoxia in a fashion similar to that observed in human and mouse eryth ropoiesis. Furthermore, guinea pig EPO did not stimulate human or mous e erythroid differentiation in vitro, whereas guinea pig erythroid pro genitors could be stimulated by human or mouse EPO, suggesting structu ral differences in guinea pig EPO and EPO receptor (EPOR) compared wit h human or mouse EPO and EPOR. These differences probably evolved afte r the guinea pig's ancestors diverged from myomorph rodents. Further c haracterization of the guinea pig EPO and EPOR should facilitate our u nderstanding of the interaction between EPO and EPOR.