Lipopolysaccharide (LPS), a well-known bacterial pyrogen, is recognized by several receptors, including the Toll-like receptor 4 (TLR4), on various cells. Which of these receptors and cells are linked to fever production is unknown. By constructing 4 mouse chimeras and studying their thermoregulatory responses, we found that all 3 phases of the typical LPS fever depend on TLR4 signaling. The first phase is triggered via the TLR4 on hematopoietic cells. The second and third phases involve TLR4 signaling in both hematopoietic and nonhematopoietic cells.
SummaryAdhesion of rat blood platelets to native rat tail collagen fibrils was studied in the electron microscope under conditions that preserved collagen-associated proteoglycans (CAPG). The CAPG molecules were aligned in chain-like configurations that encircled the fibrils with a 65 nm period; they appeared to coat the fibrils completely and extended 60-100 nm away from the fibril. The initial platelet-fibril contact occurred between the platelet glycocalyx and the CAPG of the fibrils i.e. between two surfaces with net-negative charges. When close contact was established between the fibril surface proper and the platelet membrane, CAPG were not identified in the area of contact, and the collagen-platelet distance was reduced to a ~10-12 nm wide gap traversed by delicate links in register with fibril periodicities.
Generation of Vascular Endothelial Cells and Hematopoietic Cells by Blastocyst Complementation
