Thiol proteinase inhibitors reverse the increased protein kinase C down-regulation and concanavalin A cap formation in polymorphonuclear leukocytes from Chediak-Higashi syndrome (beige) mouse

• Published in: Journal of leukocyte biology 1990-11, Vol.48 (5), p.377-381
• Main Authors: Sato, Akihiko, Tanabe, Fuminori, Ito, Masahiko, Ishida, Eiko, Shigeta, Shiro
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; calpain; Calpain - analysis; Calpain - antagonists & inhibitors; Chediak-Higashi Syndrome - blood; Concanavalin A - pharmacology; Disease Models, Animal; Down-Regulation - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Immunologic Capping - drug effects; lectins; Mice; Mice, Inbred C57BL; Myeloid cells: ontogeny, maturation, markers, receptors; neutrophils; Neutrophils - drug effects; Neutrophils - enzymology; Polynuclears; Protein Kinase C - blood
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.48.5.377

Protein kinase C (PKC) plays an essential role in intracellular signal transduction for various cell functions, including concanavalin A (Con A)‐induced cap formation. This enzyme is known to be proteolysed by calpain, which is a Ca2+ ‐dependent thiol proteinase. As reported previously, in polymorphonuclear leukocytes (PMNs) from beige mouse, the model of Chediak‐Higashi syndrome, Con A‐induced cap formation significantly increased compared with that in normal mouse. However, after pretreatment of beige PMNs with the thiol proteinase inhibitors leupeptin or E‐64, the capping decreased to normal levels. Meanwhile, Con A‐induced the translocation of PKC from the cytosolic to membrane fraction within 5 min in both mice, which is essential to the activation of this enzyme. However, after the translocation, an abnormal rapid decline in membrane‐bound PKC activity was noted in beige mouse PMNs. Both leupeptin and E‐64 also corrected the rapid decline in PKC activity observed in the beige mouse. These findings suggest that the normalization of Con A cap formation in beige mouse PMNs by the thiol proteinase inhibitors is associated with the correction of abnormality in PKC activity.