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PMID: 15331427 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Heme oxygenase-1 modulates early inflammatory responses: evidence from the heme oxygenase-1-deficient mouse.

The American journal of pathology ·Vol. 165 ·No. 3 ·2004-09-00 ·Pages 1045-53

Kapturczak MH, Wasserfall C, Brusko T, Campbell-Thompson M, Ellis TM, Atkinson MA, Agarwal A

Abstract

Induction of heme oxygenase-1 (HO-1) is protective in tissue injury in models of allograft rejection and vascular inflammation through either prevention of oxidative damage or via immunomodulatory effects. To examine the specific role of HO-1 in modulating the immune response, we examined the differences in immune phenotype between HO-1 knockout (HO-1(-/-)) and wild-type (HO-1(+/+)) mice. Consistent with previous findings, marked splenomegaly and fibrosis were observed in HO-1(-/-) mice. The lymph nodes of HO-1-deficient mice demonstrated a relative paucity of CD3- and B220-positive cells, but no such abnormalities were observed in the thymus. Flow cytometric analysis of isolated splenocytes demonstrated no differences in the proportions of T lymphocytes, B lymphocytes or monocytes/macrophages between the HO-1(-/-) and HO-1(+/+) mice. Significantly higher baseline serum IgM levels were observed in HO-1(-/-) versus HO-1(+/+) mice. Under mitogen stimulation with either lipopolysaccharide or anti-CD3/anti-CD28, HO-1(-/-) splenocytes secreted disproportionately higher levels of pro-inflammatory Th1 cytokines as compared to those from HO-1(+/+) mice. These findings demonstrate significant differences in the immune phenotype between the HO-1(-/-) and the HO-1(+/+) mice. The absence of HO-1 correlates with a Th1-weighted shift in cytokine responses suggesting a general pro-inflammatory tendency associated with HO-1 deficiency.

MeSH Terms
Animals B-Lymphocytes/metabolism CD3 Complex/metabolism Cytokines/metabolism Disease Models, Animal Female Fibrosis/enzymology,pathology Heme Oxygenase (Decyclizing)/genetics,physiology Heme Oxygenase-1 Immunoglobulin M/blood Inflammation/blood,enzymology Leukocyte Common Antigens/metabolism Lipopolysaccharides/pharmacology Lymph Nodes/pathology Macrophages/metabolism Male Membrane Proteins Mice Mice, Inbred C57BL Mice, Knockout Monocytes/metabolism Splenomegaly T-Lymphocytes/metabolism Th1 Cells/immunology,metabolism Transplantation, Homologous
Chemicals
CD3 Complex Cytokines Immunoglobulin M Lipopolysaccharides Membrane Proteins Heme Oxygenase (Decyclizing) Heme Oxygenase-1 Hmox1 protein, mouse Leukocyte Common Antigens
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kapturczak Matthias H
Division of Nephrology, University of Alabama at Birmingham, Birmingham Alabama, USA.
Wasserfall Clive
Brusko Todd
Campbell-Thompson Martha
Ellis Tamir M
Atkinson Mark A
Agarwal Anupam
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63365-2
Published
2004-09-00
Pages
1045-53
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1618611
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63365-2 PMC Full Text View journal details
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