2 GENES-CONTROLLING ACUTE-PHASE RESPONSES BY THE ANTITUMOR POLYSACCHARIDE, LENTINAN

Lentinan, a beta-1,6;1,3-glucan, is tumor-specific for transplantable mouse solid-type tumors and it also stimulates the production of acute phase proteins (APPs). The APP response to lentinan is of the delayed type (DT-APR) and differs from that to lipopolysaccharide, which is a cute. We found that the responses were genetically controlled in mice and that low responsiveness is dominant (Maeda et al. 1991). Using 123 segregants of crosses between SWR/J (a high responder) and Mus spretu s (a low responder), we analyzed the linkage between DT-APR responsive ness and the DNA polymerase chain reaction-simple sequence length poly morphism (PCR-SSLP) phenotype using 80 chromosome-specific microsatell ite markers. We identified two loci (ltn1.1 and ltn1.2) responsible fo r DT-APR. ltn1.1 is closely linked to D3Mit11 on chromosome 3 and ltn1 .2 to D11Nds9 on chromosome 11 (P < 0.001). The linkage analysis also suggested that ltn1.2 is the major determinant for DT-APR. Correlation between lentinan-specific IL-6 mRNA expression (the late expression) controlled recessively and DT-APR induction suggests that the ltn1 loc i control some process(es) of IL-6 expression in the regulation step b efore NF-IL6.