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

Am J Pathol. 2004 Sep;165(3):1045-53. doi: 10.1016/S0002-9440(10)63365-2.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • CD3 Complex / metabolism
  • Cytokines / metabolism*
  • Disease Models, Animal*
  • Female
  • Fibrosis / enzymology
  • Fibrosis / pathology
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / physiology*
  • Heme Oxygenase-1
  • Immunoglobulin M / blood
  • Inflammation / blood*
  • Inflammation / 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
  • Th1 Cells / metabolism*
  • Transplantation, Homologous


  • CD3 Complex
  • Cytokines
  • Immunoglobulin M
  • Lipopolysaccharides
  • Membrane Proteins
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Leukocyte Common Antigens