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From the Division of Nephrology,* Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and the Department of Pathology, University of Florida, Gainesville, Florida
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.
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