Monocyte and Neutrophil Chemotactic Activity at the Site of Interstitial Inflammation in Patients on High-Flux Hemodialysis or Hemodiafiltration

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Abstract

Background/Aims: We have observed a difference between patients on low-flux hemodialysis (HD) or peritoneal dialysis and patients on hemodiafiltration (HDF) or high-flux HD in the capacity of transmigrated leukocytes to mobilize CD11b in response to inflammatory stimuli compared with healthy subjects. This could be due to different interstitial chemokine concentrations. Methods: We measured concentrations of circulating and interstitial macrophage inflammatory protein-1α (MIP-1α), matrix metalloproteinase-9 (MMP-9)/neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in 10 patients on HDF or high-flux HD and 11 healthy subjects by using immunoassay. Results: The interstitial concentrations of MIP-1α, MMP-9/NGAL and IL-8 were similar in patients and healthy subjects, while the corresponding concentration of MCP-1 was significantly higher in patients on HDF or high-flux HD as compared with healthy subjects (p < 0.01). Conclusion: We suggest that an equal or higher concentration of chemokines in the interstitium in patients with HDF or high-flux HD might be one mechanism responsible for the preserved function of transmigrated leukocytes.

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Most cited references 19

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Role of interleukin-8 in neutrophil signaling.

H F Zeilhofer, W Schorr (2000)

Interleukin-8 was originally discovered as one of the first chemokines activating neutrophil granulocytes (neutrophils) after secretion by lipopolysaccharide-stimulated monocytes. A wealth of information has been gathered concerning the intracellular events mediated by interleukin-8 and the role of interleukin-8 in numerous physiologic and pathophysiologic processes. We discuss recent advances in the understanding of the initial intracellular signals elicited by interleukin-8. Detailed investigation of these events has led to the identification of subtle but significant differences in the signal transduction processes evoked by interleukin-8 receptors. In particular, much has been learned concerning differences in the cellular mechanisms leading to desensitization, internalization, and recycling of interleukin-8 receptors, and functional consequences of interleukin-8 receptor diversity are now being unraveled.

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Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients.

V Rocco, Jackie K. Cheung, Andrew Levey … (2007)

Secondary analysis of the Hemodialysis Study showed that serum beta(2)-microglobulin levels predicted all-cause mortality and that high-flux dialysis was associated with decreased cardiac deaths in hemodialysis patients. This study examined the association of serum beta(2)-microglobulin levels and dialyzer beta(2)-microglobulin kinetics with the two most common causes of deaths: Cardiac and infectious diseases. Cox regression analyses were performed to relate cardiac or infectious deaths to cumulative mean follow-up predialysis serum beta(2)-microglobulin levels while controlling for baseline demographics, comorbidity, residual kidney function, and dialysis-related variables. The cohort of 1813 patients experienced 180 infectious deaths and 315 cardiac deaths. The adjusted hazard ratio for infectious death was 1.21 (95% confidence interval 1.07 to 1.37) per 10-mg/L increase in beta(2)-microglobulin. This association was independent of the prestudy years on dialysis. In contrast, the association between serum beta(2)-microglobulin level and cardiac death was not statistically significant. In similar regression models, higher cumulative mean Kt/V of beta(2)-microglobulin was not significantly associated with either infectious or cardiac mortality in the full cohort but exhibited trends suggesting an association with lower infectious mortality (relative risk 0.93; 95% confidence interval 0.86 to 1.01, for each 0.1-U increase in beta(2)-microglobulin Kt/V) and lower cardiac mortality (relative risk 0.93; 95% confidence interval 0.87 to 1.00) in the subgroup with >3.7 prestudy years of dialysis. These results generally support the notion that middle molecules are associated with systemic toxicity and that their accumulation predisposes dialysis patients to infectious deaths, independent of the duration of maintenance dialysis.

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Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling.

Justin Moser, Andrej Khandoga, Péter Bihari … (2008)

In the present study, the role of gelatinases [matrix metalloproteinase-2 and -9 (MMP-2 and -9)] for leukocyte rolling, adherence, and transmigration was analyzed in the mouse cremaster muscle under different inflammatory conditions including ischemia-reperfusion (I/R) and stimulation with MIP-1alpha or platelet-activating factor (PAF). Using zymography, we detected a significant elevation of MMP-9 activity in response to the stimuli applied, and MMP-2 expression was not altered. However, treatment with a specific MMP-2/-9 inhibitor significantly abrogated elevated MMP-9 activity. As observed by intravital microscopy, all inflammatory conditions induced a significant increase in numbers of adherent and transmigrated leukocytes (>80% Ly-6G(+) neutrophils). Blockade of gelatinases significantly diminished I/R- and MIP-1alpha-induced leukocyte adherence and subsequent transmigration, and upon stimulation with PAF, gelatinase inhibition had no effect on leukocyte adherence but selectively reduced leukocyte transmigration. Concomitantly, we observed an increase in microvascular permeability after I/R and upon stimulation with MIP-1alpha or PAF, which was almost completely abolished in the inhibitor-treated groups. Using immunofluorescence staining and confocal microscopy, discontinuous expression of collagen IV, a major substrate of gelatinases within the perivascular basement membrane (BM), was detected in postcapillary venules. Analysis of intensity profiles demonstrated regions of low fluorescence intensity, whose size was enlarged significantly after I/R and upon stimulation with MIP-1alpha or PAF as compared with unstimulated controls. However, this enlargement was abolished significantly after inhibition of gelatinases, respectively. In conclusion, these data demonstrate that gelatinases strictly regulate microvascular permeability and BM remodeling during the early inflammatory response, whereas concomitant leukocyte recruitment is mediated by these proteases in a stimulus-specific manner.

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Author and article information

Journal

Journal ID (publisher-id): BPU

Journal ID (nlm-ta): Blood Purif

Journal ID (doi): 10.1159/issn.0253-5068

Title: Blood Purification

Publisher: S. Karger AG

ISSN (Print): 0253-5068

ISSN (Electronic): 1421-9735

Publication date Subscription-year: 2009

Publication date (Print): July 2009

Publication date (Electronic): 27 March 2009

Volume: 28

Issue: 1

Pages: 47-52

Affiliations

^aDepartment of Nephrology, Malmö University Hospital, Malmö, ^bDepartment of Clinical Immunology, Karolinska University Hospital, ^cDepartment of Oncology and Pathology, Cancer Centrum Karolinska, Karolinska University Hospital, ^dDepartment of Nephrology, Danderyd University Hospital, Karolinska Institutet, and ^eKarolinska Institutet, Stockholm, Sweden

Article

Publisher ID: 210037 Other ID: Blood Purif 2009;28:47–52

DOI: 10.1159/000210037

PubMed ID: 19325239

SO-VID: 8bf989c7-4357-4f18-9687-42460e1f483c

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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.

History

Date received : 01 September 2008

Date accepted : 07 January 2009

Page count

Tables: 4, References: 30, Pages: 6

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Monocyte and Neutrophil Chemotactic Activity at the Site of Interstitial Inflammation in Patients on High-Flux Hemodialysis or Hemodiafiltration

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Abstract

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Karger: Nephrology

Most cited references 19

Role of interleukin-8 in neutrophil signaling.

Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients.

Gelatinases mediate neutrophil recruitment in vivo: evidence for stimulus specificity and a critical role in collagen IV remodeling.

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