A novel nervous system‐induced factor inducing immune responses in the spleen

Abstract

This study relates to a novel mediator signaling between the nervous system and the spleen following an immune challenge. Using enzyme-linked immunospot and cell proliferation assays, we found that supernatants of cultured splenocytes prepared from subcutaneously trypanosome-inoculated rats and mice spleens obtained immediately after inoculation and added to naive cells significantly stimulate interferon-c production and cell proliferation compared to phosphate-buffered saline-inoculated animals. This action was abrogated by surgical denervation of the spleen. Using the fluorescent differential display technology, the gene involved in this process was identified and further cloned and its sequence was mapped to chromosome 14 (GenBank accession number: EU552928). Protein expression revealed B15 kDa molecule with biological activities similar to the cultured supernatants of splenocytes obtained directly from parasite-inoculated animals. Antibodies raised against the protein blocked the activities of both the protein and the supernatant and also recognized a band in the active supernatant with the same molecular mass as the protein. Furthermore, the protein was able to reactivate experimentally immunosuppressed cells by regaining their ability to proliferate, suggesting that such a nervous system-induced immune system-released activating agent (ISRAA) may have a potential therapeutic benefit in immunocompromised situations and in further understanding the mechanism for innate immunity commencement and action. Keywords: CNS; cytokine; innate immunity; immunosuppression A bewildering array of infectious agents and parasites gain subsistence at the expense of their hosts. Although host-parasite interplay depends on the virulence of parasites and resistance of the host, the early events of innate immunity during host-parasite interactions are very important in directing the ultimate pattern of the immune response. These early events of the innate immune response are, however, much less well characterized than the later secondary immune responses.Immune responses are not isolated from other organ systems in the body, and indeed there are various means of communication between these organ systems and the immune system. Among these communications are regulatory interactions between the nervous and the immune systems.

Effects of proteinate complex zinc on growth performance, hepatic and splenic trace elements concentrations, antioxidative function and immune functions in weaned piglets

“…In the immune system, the spleen is the largest peripheral immune organ of the pig and plays a crucial role in maintaining immune homeostasis [9]. Studies have shown that Zn is associated with antioxidative and immune functions in the liver and serum, but it is less well known whether Zn has an immunoenhancement effect on the spleen [8].…”

An interspecies conserved motif of the mouse immune system-released activating agent (ISRAA) induces proliferative effects on human cells

“…Recombinant wild type ISRAA used in this study was obtained as described previously (10). Mutated ISRAA was synthesized by site directed mutagenesis in which the predicted active site was deleted from the ISRAA gene and cloned in a pUC57 vector.…”

“…In the context of these neuroimmune interactions, in a recent study we described a novel nervous system-induced immune system-released activating agent (ISRAA)(10). It was revealed that this mediator is a signaling factor between the nervous system and the spleen following an immune challenge in mice.…”

“…The molecular mass of ISRAA was found to be ~15 kDa, along with an ability to activate immunosuppressed cells to proliferate, thus, it is has been suggested that ISRAA is a possible candidate to treat immunosuppressed patients. Furthermore, its mechanism of action may add to the understanding of how the innate immunity may function (10). The human counterpart of the mouse ISRAA is not known, therefore, this study examines the possible immune stimulating effects of the mouse ISRAA on human cells.…”

Induction of dissociated cytokine profiles by ISRAA with selective critical involvement of ERK1/2 in its signaling functions

“…EU552928) (1) and is believed to mediate signaling between the nervous and the immune system. ISRAA was initially considered to have a cytokine-like activity due to several factors, including its relatively low molecular mass, its biological effects on a broad spectrum of cell types, such as T and B cells and monocytes/macrophages, the ability of the same cell populations to respond to ISRAA by producing cytokines, such as interferon (IFN)-γ, as well as the fact that ISRAA is lined up on chromosome 14 on the mouse system where several low molecular mass cytokines are mapped (1). Although ISRAA was identified in the mouse, the alignment has shown that the molecule has conserved regions between many species (2).…”