Intercellular Adhesion Molecule-1 Expression in the Inner Ear of Rats following Secondary Immune Reaction in the Endolymphatic Sac

Abstract

Pawankar R, Tomiyama S, Jinnouchi K, Ikezono T, Nonaka M, Yagi T. Intercellular adhesion molecule-1 expression in the inner ear of rats following secondary immune reaction in the endolymphatic sac. Acta Otolaryngol (Stockh) 1998; Suppl 539: 5-14.An immunological aetiology for inner ear diseases has long been proposed. The endolymphatic sac (ES) is the only immunoprivileged site in the inner ear with a resident population of immunocompetent cells. By keyhole limpet hemocyanin (KLH) challenge into the ES of systemically pre-immunized guinea pigs, we previously demonstrated an infiltration of inflammatory cells into the perilymphatic space of the cochlea. In order to understand the mechanisms involved in the recruitment of immunocompetent cells into the inner ear, and their relation to the development of endolymphatic hydrops (EH), we investigated the expression and time-kinetics of intercellular adhesion molecule 1 (ICAM-1) in the inner ear of systemically pre-immunized rats after antigen (KLH) challenge into the ES, its relation to cell infiltration in the cochlea and subsequent development of EH. By immunohistochemistry, strong ICAM-1 expression was detected in the spiral ligament, suprastrial region, spiral prominence, spiral modiolar veins, spiral collecting venules, surface membrane of the perilymphatic compartment, perilymphatic space and ES of immunized rats, but not of control rats. ICAM-1 expression was detected at 5-6 h, peaked at 10 -15 h, and gradually reduced by 2 weeks. Cell infiltration into the cochlea started at 6-12 h and peaked at day one. By 6 h, 50% of challenged rats developed EH. This figure rose to 70% at 12 h, and then gradually reduced. However, immunoreactivity for KLH (antigen) was only detected in the ES. These results emphasize that the sac is the central immunological organ of the inner ear, and suggest that ICAM-1 may play a pivotal role in the aetiology of immune-mediated inner ear diseases through the recruitment of immunocompetent cells into the inner ear and subsequent development of EH.

The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression

“…This idea was supported by Danckwardt-Lillieström et al (11) who found microorganisms ( Mycoplasma pneumoniae ) in the lumen of the human ED, with signs of being processed. Further evidence of potential immune mechanisms was demonstrated by ablation of the ES, which lead to diminished secretion of specific antibodies in the perilymph and reduced immune activity after inner ear antigen challenge (6, 10, 12–16). Tomiyama and Harris (6) suggested that the ES plays a role for both systemic and local antibody responses.…”

The immune response after noise damage in the cochlea is characterized by a heterogeneous mix of adaptive and innate immune cells

“…In the 1980s, a series of studies performed in guinea pigs showed that an antigen-specific response to keyhole limpet hemocyanin (KLH) could be mounted within the cochlea 19,20 . When KLH was introduced into the cochlea, KLH-specific immune cells could be found in the draining lymph node and spleen [21][22][23] . Furthermore, KLH-specific antibodies were secreted in the cochlea 20,24 .…”

Evidence for a dynorphin-mediated inner ear immune/inflammatory response and glutamate-induced neural excitotoxicity: an updated analysis

“…Cochlear vascular adhesion molecule ICAM-1. Adhesion molecules within the inner ear also play an important role in the extravasation of inflammatory cells from the systemic circulation (Gong et al 1998;Pawankar et al 1998). In cochlear microvascular endothelial cells, ICAM-1 is important for leukocyte cellular arrest, leukocyte adhesion, and leukocyte extravasation (Steiner et al 2010).…”

“…In cochlear microvascular endothelial cells, ICAM-1 is important for leukocyte cellular arrest, leukocyte adhesion, and leukocyte extravasation (Steiner et al 2010). After an immune challenge, ICAM-1 is upregulated within the following: 1) the spiral ligament, 2) the endothelial cells of the SMV and its collecting venules, 3) the capillaries of the spiral ganglion, and 4) the surface membranes (endosteal cells) and perilymph of the scala tympani (Gong et al 1998;Pawankar et al 1998).…”