Abstracts (complete list) - Wissenschaft Online

Claudia Sievers, Kasia Nasilowska, Kerstin Wolk, Robert Sabat, Hans-Dieter Volk,
Christian Meisel
HO-1 inhibits constitutive and IFNg-induced HLA-DR
expression on myeloid antigen-presenting cells via inhibition
of IFNg receptor signalling and down-regulation of CIITA
expression
Strong and prolonged systemic immunodepression after surgery and major trauma,
characterised by monocyte deactivation and T cell dysfunction, may predispose critically
ill patients to infectious complications. The mechanisms that induce and sustain this
condition are still incompletely understood. Previous studies showed increased
expression of heme oxygenase-1 (HO-1) in peripheral blood leukocytes in a subset of
surgical patients who developed post-operative long-lasting immunodepression and
infectious complications. HO-1 is a stress-inducible heat shock protein with potent antiinflammatory
activities. We hypothesized that increased expression of HO-1 may play a
role in the induction of long-lasting immunodepression. Here, we investigated the
effects of HO-1 on APC and T cells function in vitro by using the specific HO-1 inducer
cobalt protoporphyrin IX (CoPP). CoPP increased HO-1 expression in human monocytes
and monocyte-derived dendritic cells, but not in lymphocytes. HO-1 induction resulted
in diminished constitutive surface MHCII expression on myeloid APC, while MHCI
expression was unaffected. HO-1 overexpression in monocytes resulted in decreased
transcription of CIITA and other accessory genes essential for MHCII protein stability
and peptide loading, including CD74, HLA-DM and Cathepsin S. Decreased STAT-1
phosphorylation in response to IFNg in CoPP-treated monocytes suggests that HO-1
impairs cytokine-induced up-regulation of HLA-DR expression also by interfering with
cytokine-receptor signalling. Enhanced expression of HO-1 in APC resulted in diminished
antigen-dependent T-cell cytokine production and proliferation. Taken together these
data indicate that increased HO-1 activity may partake in the induction of
immunodepression in critically ill patients.