Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells The MRL/lpr mouse, which has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, shows an accumulation of abnormal immunocompetent cells and SLE-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of injecting MRL/lpr spleen cells on the development of SHL in severe combined immunodeficient (SCID) mice, which originally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology were, indeed, transferred to the SCID mice by the injection of spleen cells from the MRL/lpr mice. These findings suggest that cell-mediated immunity is involved in the development of SHL and cochlear pathology.

Factors related to inflammation, including platelet-activating factor (PAF), apparently have a role in chronic otitis media with effusion. PAF is metabolized to the biologically inactive lyso-PAF by the enzyme PAF-acetylhydrolase (PAF-AH). We have obtained evidence that PAF-AH activity is present in human middle ear effusions in patients with chronic otitis media with effusion. The present study revealed the enzyme in human middle ear effusions to be the plasma type PAF-AH. We suggest that PAF-AH may be involved in regulating inflammation in the middle ear by inactivating PAF, the potent proinflammatory autacoid.

Changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human mucosal microvascular endothelial cells (HMMECs) from nasal inferior turbinate were measured using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy. Histamine caused a transient increase in intracellular free Ca2+ in cell populations and in individual cells, followed by a decrease to a sustained elevation. Histamine (100 microM) elevated [Ca2+]i in HMMECs up to 563 +/- 20 nM from a resting level of 60 +/- 45 nM (means +/- SD, n = 31). Promethazine (a histamine H1 receptor antagonist) inhibited [Ca2+]i increase during histamine stimulation, whereas cimetidine (a H2 receptor antagonist) and thioperamide (a H3 receptor antagonist) showed no inhibition. These results suggest that the histamine increase [Ca2+]i in HMMECs induces both a Ca2+ release from stores and a Ca2+ influx through activation of the H1 receptor.

Human mucosal microvascular endothelial cells (HMMECs) were isolated and cultured from the mucosa of nasal inferior turbinates. These cells were identified by human factor-VIII antigen and UEA-I. We also investigated alterations in intracellular calcium concentration [Ca2+]i, in HMMECs using the Ca(2+)-sensitive dye fura-2. Depolarization by high K+ (150 mM) induced no changes in [Ca2+]i in HMMECs, thereby indicating the lack of voltage-dependent Ca2+ channels in these cells. Extracellular ATP increased [Ca2+]i in HMMECs both in the presence and absence of extracellular Ca2+. These results suggest that ATP may induce a release of Ca2+ from intracellular stores in HMMECs. Adenosine induced no changes in [Ca2+]i in HMMECs. It is thus likely that HMMECs obtained from the nasal inferior turbinate may carry P2-purinoceptors but not P1-purinoceptors.

Effects of capsaicin on autonomic nerves in the nasal mucosa and olfactory bulb of toluene diisocyanate sensitized guinea pigs were studied using immunocytochemistry. In the nasal mucosa, substance P (SP)- and tyrosine hydroxylase (TH)-like immunoreactive (SPI and THI) fibers seemed to decrease after capsaicin application. Calcitonin gene-related peptide (CGRP)-like immunoreactive (CGRPI) fibers did not show obvious alterations. In the olfactory bulb, SPI and CGRPI fibers were few and the effects of capsaicin on those fibers were difficult to evaluate. THI fibers seemed not to be affected by capsaicin. It is suggested that capsaicin affects not only sensory nerves but that it also impacts on THI sympathetic nerves in the nasal mucosa.