With agonist binding, the TLR4 dimerizes and undergoes a conformational change required for the recruitment of signaling molecules [40] , such as the adaptor molecules myeloid differentiation protein 88 (MyD88) and Toll-interleukin-1(IL-1) receptor Figure 2 . Representative dark-field micrographs of platelets from a WT mouse taken immediately before or after 30 and 60 min. incubation of the blood with 500 ng/ml LPS. Prior to LPS application, platelet aggregates (of more than 5 platelets) were absent, and most platelets were discoid shaped (Left panels). At 30 and 60 minutes incubation with saline, platelet morphology did not change (Top panels); whereas, large aggregates of irregularly-shaped platelets were observed in those incubated with LPS (bottom panels, inset shows platelets with pseudopodia). Each bar represents 5 mm. Similar results were observed with blood from two additional animals (n = 3). doi:10.1371/journal.pone.0025504.g002 domain containing adaptor inducing interferon-b (TRIF), which mediate MyD88 dependent or independent pathway respectively [41, 42] . LPS activates both MyD88 and TRIF pathways, which are important in the TLR4 mediated intracellular signaling [42] . The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Furthermore, leukocyte antigen expression on platelet was reduced by inhibition of MyD88-and TRIF-dependent pathways alone or in combination. These signaling pathways may be potential molecular targets to inhibit infection/inflammation induced interactions among formed elements in the blood.