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      Heme-Containing Proteins Suppress Lymphatic Pumping


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          Red blood cells (RBCs) and lysate products (erythrolysate) are consistently observed in lymph draining inflammatory reactions and from tissues subjected to trauma or surgical procedures. We determined previously that erythrolysate modulates lymphatic pumping by altering the pressures over which the lymph pump is active. The purpose of this study was to test the hypothesis that oxyhemoglobin was the active material within erythrolysate. To quantitate lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure could be applied to the vessels. This procedure stimulated pumping activity. Erythrolysate was prepared from sheep RBCs by lysis in Tris buffer and a portion of this was purified by column chromatography using DEAE-Sephadex A-50. Both the purified hemoglobin (10<sup>–5</sup> M) and crude erythrolysate (the latter diluted appropriately in Krebs solution to contain 10<sup>– 5</sup> M hemoglobin) reduced lymphatic fluid pumping approximately 70% over a period of 2 h. To determine whether this activity was due to the heme or the protein portion of the molecule, we compared the activity of purified oxyhemoglobin with that of its oxidized methemoglobin derivative. This was achieved by conversion with potassium ferricyanide. Methemoglobin was inactive, suggesting that the heme portion was important for the lymphatic effect. Further confirmation of this observation was provided by experiments with myoglobin which was purified from sheep heart. Oxymyoglobin, which shares an identical heme but has a different protein component, inhibited lymphatic pumping, when tested on the bovine lymphatics. These data suggest that oxyhemoglobin is the component within erythrolysate that modulates lymphatic pumping and we speculate that its presence in lymph (and the presence of other heme-containing proteins) may impair the ability of lymphatic vessels to drain liquid and protein from the tissue spaces and facilitate edema formation.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          23 September 2008
          : 29
          : 3
          : 248-255
          Trauma Research Program and Departments of Pathology and Surgery, Reichmann Research Building, Sunnybrook Health Science Centre, Toronto, Canada
          158939 J Vasc Res 1992;29:248–255
          © 1992 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          : 26 August 1991
          : 10 January 1992
          Page count
          Pages: 8
          Research Paper

          General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
          Oxyhemoglobin,Myoglobin,Pumping activity,Methemoglobin,Hemoglobin,Lymphatic vessel


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