Regulation of Spleen Growth and Sequestering Function*

Jacob, Harry S.; MacDonald, Richard A.; Jandl, James H.

doi:10.1172/jci104832

Cited by 87 publications

(29 citation statements)

References 40 publications

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“…14,35 This provokes a transient dehydration and increased loss of intracellular potassium that is only partially offset by an increase in intracellular sodium. 14,34,36,37 If such a process takes place in the circulating LPC-treated RBCs, this would lead to a decrease in cell volume, creating a more favorable S/V ratio and enabling the surface-deficient RBCs to remain in the circulation. This hypothesis is supported by the fact that LPC-treated RBC dimensions were similar at T0 and T40 and both were significantly lower than that of untreated RBCs ( Figure 4A-C).…”

Section: Discussionmentioning

confidence: 99%

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Safeukui

Buffet

Deplaine

et al. 2012

Blood

122

139

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IntroductionDuring their 120-day life span, human RBCs repeatedly traverse capillaries of the vascular bed and interendothelial slits of the venous sinus of spleen red pulp, both of which are narrower than their smallest dimension. 1 This necessitates maintenance of the ability of RBCs to undergo repeated, extensive, and reversible deformations. Repeated major membrane deformations induce ion and water permeability changes in the RBCs. [2][3][4][5] The biconcave discoid shape endows the human RBC with an advantageous surface area-to-volume (S/V) ratio, allowing the cell to undergo marked deformations while maintaining a constant surface area. [6][7][8] A reduced RBC S/V ratio has long been recognized to contribute to pathogenesis of several RBC disorders, 9-11 including hereditary spherocytosis (HS), the most common cause of inherited chronic hemolytic anemia in Northern Europe and North America, with an estimated incidence of 1 in 2000. 11 The clinical presentation of HS can range from mild to severe hemolytic anemia. 12,13 The molecular basis of HS is heterogeneous, the common denominator being the loss of HS RBC membrane surface area due to specific molecular defects in several membrane proteins (␣ or ␤ spectrin, ankyrin, protein 4.2, and protein band 3), which result in the loss of cohesion between the lipid bilayer and the membrane skeleton. 10,11,14,15 The loss of membrane surface area results in the transformation of the biconcave discoid shape, first to a stomatocyte and finally to a spherocyte, with a progressive reduction in cellular deformability.Although a major role for the spleen in pathogenesis of HS is well established, 16 there are currently no data on the quantitative relationship between the extent of surface area loss and the extent of splenic entrapment. The only indirect evidence comes from early studies documenting reduced survival of Cr 51 -labeled spherocytes infused into healthy recipients, whereas the survival of normal RBCs in HS subjects was normal. [17][18][19] This implied that the reduced life span and splenic entrapment was an intrinsic feature of HS RBCs. Unfortunately, because neither the surface area nor the S/V ratio of infused spherocytes was measured in these studies, the extent of membrane surface area loss (or reduced S/V ratio) that leads to splenic retention of altered RBCs remains undefined. As a result, there is no predictive biologic parameter with which to estimate the risk of splenic entrapment of spherocytic cells and the ensuing anemia. Previously, we addressed this important issue using the isolated human spleen system 20 perfused with human RBCs with defined extents of surface area loss.RBCs with defined loss in membrane surface area can be generated experimentally by treatment with lysophosphatidylcholine (LPC). 6,7 By initially accumulating exclusively in the external leaflet of the RBC lipid bilayer, LPC induces in a dose-dependent manner echinocytosis There is an Inside Blood commentary on this article in this issue.The online version of this article contai...

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Section: Discussionmentioning

confidence: 99%

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Safeukui

Buffet

Deplaine

et al. 2012

Blood

122

139

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“…Clearance studies performed from 1 to 8 weeks post-splenectomy did not reveal any evidence that the liver acquired greater capacity to clear IgG-sensitized cells over the course of time. In this model the animals did not have an ongoing hemolytic process to stress the RES which might be necessary for the liver to increase its sequestering ability (19,20).…”

Section: Discussionmentioning

confidence: 99%

Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes

Atkinson¹,

Schreiber²,

Frank³

1973

J. Clin. Invest.

105

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“…The direction of tissue transfer was from O to A, an incompatibility which had been demonstrated to be relatively safe in the performance of renal transplantation inasmuch as the homograft is not placed in contact with preformed host hemagglutinins. 12,13 With hepatic homografts, such a breach of blood group incompatibility may be less safe, since the liver possesses erythroclastic activity 14 and might react against the recipient red cells. A graft-versus-host reaction under these circumstances is a distinct possibility, manifesting as a hemolytic reaction.…”

Section: Human Homografts After Recipient Hepatectomymentioning

confidence: 99%

Experimental and Clinical Homotransplantation of the Liver*

Starzl¹,

Marchioro²,

Huntley³

et al. 1965

Annals of the New York Academy of Sciences

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Until the present time, whole-organ hepatic homotransplantation has been a disappointing procedure, both in experimental animals and in man. The operation itself carries a high immediate risk, especially in the dog, which is peculiarly subject to an anoxic hepatic injury termed "outflow block." In reported canine experiments, the majority of animals have failed to recover from the acute effects of operation. Because of the fact that it has not been possible to obtain a consistently satisfactory preparation, evaluations of the efficacy of immunosuppressive regimens for the prevention of rejection have never been published.In the following remarks, attention will be directed to the influence of therapy with azathioprine, or azathioprine plus prednisone, upon the rejection process in dogs and in five patients receiving hepatic homografts after removal of their own livers. Since efforts to obtain long-term survival were eventually futile in both groups, an analysis of the reasons for failure will be attempted. Finally, alternative solutions will be presented which are designed to avoid the many pitfalls that have thus far precluded success. Orthotopic Homotransplantation in Dogs Using Living DonorsTwenty-five dogs had replacements of their own livers with hepatic homografts obtained from living canine donors, employing a previously described technique. 1 The donor organs were removed from healthy animals, which had been cooled to 30-32° C. At the moment the hepatic arterial circulation was interrupted, perfusion of the liver was begun with chilled lactated Ringer's solution (10-15° C.) through the portal vein. The inferior vena caval and portal systems of the recipient dog, which must be temporarily occluded during insertion of the liver, were joined with a temporary portacaval anastomosis and then decompressed with a single external by-pass (FIGURE 1) from the inferior to the superior vena caval systems. 1 The upper vena caval, lower vena caval, hepatic arterial, and portal venous anastomoses were done in that order, and the temporary portacaval anastomosis subsequently taken down so that the vascular supply to the homograft was essentially normal. 1 Internal biliary drainage was provided with a loop cholecystenterostomy. Two to 10 mg./kg. per day of azathioprine were given postoperatively to all animals (FIGURES 2 and 3), supplemented in a few cases with 20 to 100 mg. per day of subcutaneous prednisolone or prednisone (FIGURE 3).Eleven of the 25 animals lived for less than three days after operation (TABLE 1). Ten of the early deaths were due to hemorrhage, either into the peritoneal cavity or the * Aided by Grants A-6283, A-6344, HE07735, AM 07772, AI 04152, and OG 27 from the U. S. Public Health Service. † Markle Scholar. NIH Public Access Author ManuscriptAnn N Y Acad Sci. Author manuscript; available in PMC 2011 August 11. gastrointestinal tract, and in all of these cases there was some evidence of hepatic outflow block. With this syndrome, the liver becomes swollen and congested, and frequently hemorr...

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Regulation of Spleen Growth and Sequestering Function*

Cited by 87 publications

References 40 publications

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen

Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes

Experimental and Clinical Homotransplantation of the Liver*

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