Heme oxygenase-1 modulates early inflammatory responses: evidence from the heme oxygenase-1-deficient mouse.
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.
Division of Nephrology, University of Alabama at Birmingham, Birmingham Alabama, USA.
Matthias H
MH
Kapturczak
Clive
C
Wasserfall
Todd
T
Brusko
Martha
M
Campbell-Thompson
Tamir M
TM
Ellis
Mark A
MA
Atkinson
Anupam
A
Agarwal
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000201:enzymology / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000502:physiology*; D051547:Heme Oxygenase-1; D007075:Immunoglobulin M / Q000097:blood; D007249:Inflammation / Q000097:blood* / Q000201:enzymology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism; D013163:Splenomegaly; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D014184:Transplantation, Homologous
D017252:CD3 Complex; D016207:Cytokines; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D017493:Leukocyte Common Antigens