Concomitant Vascular Calsequestrin 2 overexpression and leukocytes transmigration in a rat model of skeletal muscle traumatic inflammatory injury

Abstract

The network of molecular mediators involved in the transmigration of leukocytes to inflamed tissues has been expanding with the identification of new molecules involved in the inflammatory response. We have previously shown using a rat model that Protein Disulfide Isomerase PDIA4 (ERP72) is involved in the inflammatory response to skeletal muscle traumatic injury. In this paper, we report observations suggesting that calsequestrin 2 (CASQ2), another member of the thioredoxin/PDI family, might contribute to the inflammatory response that leads to adhesion and transmigration of leukocytes into injured skeletal muscle. Indeed, real time PCR assay showed that the expression level CASQ2 is significantly enhanced [p<0.01] in the mechanically injured muscle. Immunohistological and immunofluorescence analysis showed that CASQ2 but not CASQ1 is expressed in the vessels present in the muscle-injured area. In addition, CASQ2 overexpression and PMN transmigration to the inflamed muscle injury are concomitant. This overexpression occurs most likely in the smooth muscle of the inflamed vessel. These observations together with the known Ca2+ buffering role of CASQ2 suggest that the protein contributes to the inflammatory process by providing the Ca2+ needed to activate the inflammasome and the leukocytes adhesion molecules which enhances transmigration of inflammatory cells into the injured muscle.