Figure 2
Figure 2. Structure-function correspondences in the slow, open microcirculation. (A) On human spleen sections, the medium-sized central artery (CA) is surrounded by white pulp (here, a lymphoid nodule; LN) made of densely packed white cells, between which no RBCs circulate. In the perifollicular zone (PFZ) that surrounds the white pulp, RBCs are visible within flat, concentric microcirculatory spaces. In the red pulp (RP), typical sinuses (S) are observed. RBCs engaged in the fast, closed circulation transit through the PFZ, whereas RBCs in the open microcirculation navigate slowly in the RP cords before returning to the blood vascular bed by crossing the wall of sinuses. Because direct by-passes exist between the PFZ and sinuses, sinus lumens (sl)—though located in the RP—collect both the fast (closed) and the slow (open) microcirculations (Giemsa-stained human spleen section ×400). (B) Macrophages account for almost half the volume of the cords (co), although approximately 10% of them can be found in the sinus lumen (sl, immunohistochemistry of an isolated-perfused human spleen section using an anti-CD68 primary antibody revealed with a peroxidase secondary antibody, ×400). Because the RP accounts for 75% of spleen volume, an average 150-g human spleen contains approximately 50 g (or 50 mL) of macrophages (ie, approximately 100 times greater than the average 0.5-mL volume of monocytes circulating in the vascular beds). (Ci) The visualization of sinus walls on histologic sections is facilitated by PAS (phosphatase acid shift) staining that highlights the peculiar basal fibers of sinuses, providing a clear separation between cords (co) and sinus lumens (sl) (isolated-perfused human spleen ×1000). The sinus wall is made of elongated endothelial cells surrounded by helical basal fibers. (Cii) In a patient treated with artemisinin derivatives, if the parasite load is high, parasite remnants either pitted from their host RBCs or retained with their host RBC delineate the abluminal side of the sinus wall (D1, PAS-stained post mortem spleen sample, ×400). (Di) On transmission electron microscopy (TEM), the periodic disposition and homogenous aspect of basal fibers (pseudocolored purple), as well as elongated shape of sinus endothelial cells (pseudocolored blue), allows an accurate orientation (isolated-perfused human spleen, ×2000). (Dii) When pitted from an RBC squeezing through an inter endothelial slit in a sinus wall, P falciparum remnants are deposited on the abluminal side of the sinus (PAS-stained section of an isolated-perfused human spleen challenged with artesunate-exposed P falciparum–infected RBCs, ×1000, inset ×2000). These observations confirm that pitting occurs exclusively or very predominantly, whereas RBCs cross the sinus wall and illustrates the unidirectional aspect of sinus wall crossing by RBCs—from cords to sinus lumen.

Structure-function correspondences in the slow, open microcirculation. (A) On human spleen sections, the medium-sized central artery (CA) is surrounded by white pulp (here, a lymphoid nodule; LN) made of densely packed white cells, between which no RBCs circulate. In the perifollicular zone (PFZ) that surrounds the white pulp, RBCs are visible within flat, concentric microcirculatory spaces. In the red pulp (RP), typical sinuses (S) are observed. RBCs engaged in the fast, closed circulation transit through the PFZ, whereas RBCs in the open microcirculation navigate slowly in the RP cords before returning to the blood vascular bed by crossing the wall of sinuses. Because direct by-passes exist between the PFZ and sinuses, sinus lumens (sl)—though located in the RP—collect both the fast (closed) and the slow (open) microcirculations (Giemsa-stained human spleen section ×400). (B) Macrophages account for almost half the volume of the cords (co), although approximately 10% of them can be found in the sinus lumen (sl, immunohistochemistry of an isolated-perfused human spleen section using an anti-CD68 primary antibody revealed with a peroxidase secondary antibody, ×400). Because the RP accounts for 75% of spleen volume, an average 150-g human spleen contains approximately 50 g (or 50 mL) of macrophages (ie, approximately 100 times greater than the average 0.5-mL volume of monocytes circulating in the vascular beds). (Ci) The visualization of sinus walls on histologic sections is facilitated by PAS (phosphatase acid shift) staining that highlights the peculiar basal fibers of sinuses, providing a clear separation between cords (co) and sinus lumens (sl) (isolated-perfused human spleen ×1000). The sinus wall is made of elongated endothelial cells surrounded by helical basal fibers. (Cii) In a patient treated with artemisinin derivatives, if the parasite load is high, parasite remnants either pitted from their host RBCs or retained with their host RBC delineate the abluminal side of the sinus wall (D1, PAS-stained post mortem spleen sample, ×400). (Di) On transmission electron microscopy (TEM), the periodic disposition and homogenous aspect of basal fibers (pseudocolored purple), as well as elongated shape of sinus endothelial cells (pseudocolored blue), allows an accurate orientation (isolated-perfused human spleen, ×2000). (Dii) When pitted from an RBC squeezing through an inter endothelial slit in a sinus wall, P falciparum remnants are deposited on the abluminal side of the sinus (PAS-stained section of an isolated-perfused human spleen challenged with artesunate-exposed P falciparum–infected RBCs, ×1000, inset ×2000). These observations confirm that pitting occurs exclusively or very predominantly, whereas RBCs cross the sinus wall and illustrates the unidirectional aspect of sinus wall crossing by RBCs—from cords to sinus lumen.

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