ROLE OF TNFR1 AND TNFR2 IN TNF-INDUCED PLATELET CONSUMPTION IN MICE

An injection of TNF in mice induced profound thrombocytopenia, due to an increase of platelet consumption, that was evident after 1 h and la sted for 3 days. This process was evident in mice that were geneticall y deficient in TNFR2 (p75) but not in mice lacking TNFR1 (p55), indica ting that the process is mediated by TNFR1-bearing cells. To explore t he site of action of TNF, labeled platelets from TNFR1 -/- or +/+ dono rs were transferred to TNFR1 -/- or +/+ recipients. TNF induced the co nsumption of platelets from TNFR1 -/- donors when injected into +/+ re cipients, while platelets from +/+ donors were not consumed when prese nt in TNFR1 -/- recipients; this finding indicates that TNF acts on th e TNFR1 of host cells but does not act on platelets. The expression of TNFRs is consistent with this interpretation, since TNFRs were not de tected on platelets by how cytometry, In megakaryocytes, the expressio n of TNFR1 was detected by immunohistochemistry. These results indicat e that TNF induces platelet consumption by acting not on platelets dir ectly but on the TNFR1 of other cells, presumably increasing the relea se of factors with agonist activity for platelets.