![]() Indeed, when we tested mouse and human sera for AIM by immunoblotting under non-reducing conditions, although the molecular weight of AIM is 37 kDa in humans and 42 kDa in mice, the AIM signal was only observed at a position identical to that of the pentameric IgM (>500 kDa). 11 first reported that the blood IgM immune complex (IC) contains AIM, which was determined using mass spectrometric analysis of co-precipitates with IgM. In contrast, AIM levels in men are fairly steady at all ages, similar to those found in women over 50 years of age. ![]() 10 We analyzed serum AIM levels in more than 20 000 healthy human individuals and found that AIM levels are high in young women (teens to 20s) and gradually decrease with increasing age until ~50 years of age, after which they are fairly steady. 10 reported that the transcription factor MafB is also involved in the regulation of AIM mRNA expression. 6 AIM is mainly produced by tissue macrophages, including liver Kupffer cells and peritoneal resident macrophages, and is transcriptionally regulated by nuclear receptor liver X receptor/retinoid X receptor heterodimers. 1, 5, 6 To the best of our knowledge, human and mouse AIM proteins are functionally equivalent. 4 The AIM protein sequence is well conserved between humans and mice, with 78% amino-acid homology, but exhibits variations in its glycosylation state. 1, 2, 3 AIM belongs to the scavenger receptor cysteine-rich (SRCR) superfamily, which all share a highly conserved cysteine-rich domain of ~100 amino acids. 1 Serum AIM levels are relatively high (~5 μg/ml) in humans and mice. Interestingly, we recently found that circulating immunoglobulin M (IgM) behaves as such a carrier and that its primary aircraft is the apoptosis inhibitor of macrophage (AIM) protein.ĪIM, also known as CD5-like antigen (CD5L), is a circulating protein initially identified as an apoptosis inhibitor that supports the survival of macrophages against different types of apoptosis-inducing stimuli. However, to conserve the time and energy required for effector activation, it may be more efficient to maintain effectors on stand-by in the blood and to release them on demand in an active form against the target, similar to fighter jets being launched from a large aircraft carrier. Conversely, in some cases, effectors that have already been generated and stored within cells are rapidly released in response to more acute events this action is typically observed in immune cells secreting cytokines during infection or Langerhans β cells emitting insulin in response to hyperglycemia. In most cases, the production of effector molecules is rapidly upregulated via an increase in the transcription of mRNA for the relevant molecules. Various biological cascades respond to alerting signals against life-threatening events, such as tissue injury. The regulation of AIM–IgM binding, resulting from the discovery of reciprocal actions between AIM and IgM, could lead to the development of novel therapies against different diseases. Conversely, association with AIM inhibits IgM binding to the Fcα/μ receptor on follicular dendritic cells at the splenic germinal center, thereby protecting the IgM immune complex from Fcα/μ receptor-mediated internalization, which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody production. Interestingly, cats exhibit a deficiency in AIM release from IgM, which may increase their susceptibility to renal failure. Most typically, upon induction of acute kidney injury (AKI), IgM-free AIM is filtered by the glomerulus in the kidney, which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules, thereby facilitating the repair of kidney injury. Under different disease conditions, AIM can dissociate from IgM locally or systemically to exert its function, inducing the removal of various biological debris such as excess fat, bacteria, cancer cells or dead cell debris. On the other hand, IgM also behaves as a carrier of the apoptosis inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated form of AIM in the blood through this association. Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens thus, it is involved in both beneficial and detrimental immune responses, including protection from infection and the progression of autoimmunity.
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