Administration of anti-type II collagen antibody sustains footpad swelling of mice caused by a delayed-type hypersensitivity reaction and induces severe arthritis.

Delayed-type hypersensitivity (DTH) is an immune reaction induced by antigen. In the mice footpads at which DTH is elicited, transient swellings which usually peaks at 24-48 h after the antigen challenge are observed. We found that the footpad swellings of mice are sustained for at least 7 days after the antigen challenge if the mice were injected with anti-type II collagen monoclonal antibody (anti-CII MoAb) before the antigen challenge. A histological section of the swelled hindpaw revealed that severe joint inflammation and bone destruction was induced. These features were not observed in the footpads of the DTH-induced mice. Analysis of the inflammatory reaction induced by both the DTH and the anti-CII MoAb injection, here named as DTH arthritis, revealed the following: (1) DTH arthritis is elicited in an antigen-specific manner; and (2) the development of DTH arthritis is mediated by antigen-specific T cells, especially CD4+ T cells.

Inhibition of the ryanodine receptor calcium channel in the sarcoplasmic reticulum of skeletal muscle by an ADP/ATP translocase inhibitor, atractyloside.

The effects of an inhibitor of ADP/ATP translocase (AAT) mainly expressed in the mitochondria inner membrane, atractyloside (ATR), on the gating property of the Ca2+ channels in the sarcoplasmic reticulum (SR) vesicles from the rabbit skeletal muscle were investigated using ion flux measurement and single channel recording. At 10 microM of cytoplasmic Ca2+, ATR decreased the rate constant of choline+ influx through the Ca2+ channels up to about 60% and perfectly inhibited about half the population of single Ca2+ channels incorporated into planar bilayers. Furthermore, the inhibition of the Ca2+ channels by ATR was effective at lower Ca2+. These results support the previous results that AAT exists in the skeletal muscle SR and plays a key role in the Ca2+ mobilization of the skeletal muscle cell [Yamaguchi, N., and Kasai, M. (1998) Biochem. J. 335, 541-547], and the number of Ca2+ channels regulated by AAT is thought to depend on the cytoplasmic Ca2+ concentration.

Biochemical characterization of calsequestrin-binding 30-kDa protein in sarcoplasmic reticulum of skeletal muscle.

Calsequestrin (CSQ)-binding 30-kDa protein in the sarcoplasmic reticulum (SR) of rabbit skeletal muscle was purified from the junctional face membrane (JFM) in the SR. Analysis of proteins which bound to the affinity column conjugated with the purified 30-kDa protein was performed. As a result, in the heavy fraction of the SR (HSR), four proteins including CSQ proved to be adsorbed on the column, and in the JFM, one protein, whose molecular weight was about 25-kDa. was mainly adsorbed. Furthermore, the same 25-kDa protein was found to be adsorbed on the CSQ affinity column. This 25-kDa protein is probably the CSQ-binding 26-kDa protein (junctin) recently reported [Jones, L. R., et al. (1995) J. Biol. Chem. 270, 30787] judging from the molecular weight and the CSQ-binding property. These results suggest that three proteins, CSQ, 30-kDa protein, and 25-kDa protein, form a protein complex in the terminal cisternae of the SR.