However, NK cells also appear to mediate tissue damage during the acute phase of sepsis.
Consequently, Th1 cells, long thought to mediate tissue damage, might only be involved in the initiation of tissue damage, without playing a decisive role.
ANCA targeting primary granule antigens expressed on the neutrophils are known to elicit neutrophil activation and degranulation and subsequently mediate tissue damage [ 24– 26].
As resident brain macrophages, microglia function as sentries, but when activated they can mediate tissue damage, a scenario considered for several CNS inflammatory disorders (10, 15, 27).
54 Neutrophils mediate tissue damage by cytotoxic and proinflammatory cytokine production and can infiltrate the organ within hours after surgical trauma or ischemia has been established.
Moreover, immune-mediated liver injury is a consequence of the recruitment of effector leukocytes to the liver where they mediate tissue damage.
TRAIL is upregulated on SLE T cells [ 45, 46] and in lupus serum [ 47], and has been proposed to mediate tissue damage [ 46] and nephritis [ 48].
Furthermore, the elevation in catecholamine levels may generate free radicals [ 24], which may be cytotoxic and mediate tissue damage by injuring cellular membranes and releasing intracellular components.
Antibodies may mediate tissue damage when they form immune complexes and recruit cytotoxic effector cells, such as macrophages via their Fcγ receptors (FcγRs) or by activating complement [ 34].
Consequently, in AKU the chronic accumulation of HGA and its auto-oxidized derivatives may initiate a variety of reactions that promote inflammatory responses and mediate tissue damage.
Although controversial, both stages are considered to independently mediate tissue damage via the production of directly injurious reactive oxygen species (ROS) [ 24], as well as substances that modulate a local and systemic inflammatory response.
