Mouse anti-Human CD5L monoclonal antibody, clone 2D9

Apoptosis inhibitor of macrophage (AIM, encoded by cd5l) is a multi-functional circulating protein that has a beneficial role in the regulation of a broad range of diseases, some of which are ameliorated by AIM administration in mice. In blood, AIM is stabilized by association with IgM pentamers and maintains its high circulating levels. The mechanism regulating the excessive accumulation of blood AIM remains unknown, although it is important, since a constitutive increase in AIM levels promotes chronic inflammation. Here we found a physiological AIM-cleavage process that induces destabilization of AIM and its excretion in urine. In blood, IgM-free AIM appeared to be cleaved and reduced in size approximately 10 kDa. Cleaved AIM was unable to bind to IgM and was selectively filtered by the glomerulus, thereby excreted in urine. Amino acid substitution at the cleavage site resulted in no renal excretion of AIM. Interestingly, cleaved AIM retained a comparable potency with full-length AIM in facilitating the clearance of dead cell debris in injured kidney, which is a key response in the recovery of acute kidney injury. Identification of AIM-cleavage and resulting functional modification could be the basis for designing safe and efficient AIM therapy for various diseases.

The factors involved in disturbing host homeostasis during sepsis are largely unknown. We sought to determine the immunopathological role of apoptosis inhibitor of macrophage (AIM)/CD5L in sepsis. Here, we show that blockade of AIM led to significantly increased survival after experimental sepsis, and it decreased local and systemic inflammation, reduced tissue injury, and inhibited bacterial dissemination in the blood, in particular at later time points. Supplementation of recombinant AIM in sepsis resulted in increased tissue injury, amplified inflammation, increased bacteremia, and worsened mortality. Interestingly, the most important difference in the production of cytokines and chemokines after in vivo AIM blockade or AIM administration during sepsis was IL-10. In vitro, AIM enhanced IL-10 production from macrophages, neutrophils, or lymphocytes. In vivo, the beneficial effects of AIM blockade and the detrimental effects of AIM addition on experimental sepsis were ablated by treatment with recombinant IL-10 and neutralizing anti-IL-10 antibodies, respectively. This study is the first to identify AIM as an important mediator in disturbing host homeostasis in sepsis.