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

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阅读量:

48

摘要:

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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DOI:

10.1016/S0002-9440(10)63365-2

被引量:

745

年份:

2004

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2008
被引量:81

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