Expression of Tyrosine Phosphorylated ZAP–70, a Lymphoid Tyrosine Kinase, in Human Lacrimal Gland Tissue

Abstract

Abstract: : Purpose: Immunohistochemical detection of phosphorylated ZAP–70 expression in human lacrimal gland and adenoid cystic carcinoma. ZAP–70, a member of the syk family of protein tyrosine kinases, has been described as a lymphoid protein tyrosine kinase (PTK). When ZAP–70 is phosphorylated, ZAP–70 has increased kinase activity that activates downstream signaling events in T and NK cells. Expression of phosphorylated of ZAP–70 has not been previously demonstrated to occur in ocular tissues. Methods: ZAP–70 expression was detected by immunohistochemistry using antibody against tyrosine phosphorylated (activation–specific) ZAP–70 (Cell Signaling Technology, Beverly, MA) on normal lacrimal gland. Phosphorylated ZAP–70 expression was also examined on adenoid cystic carcinoma tissue pre– and post–treatment with intracarotid cisplatin and intravenous doxorubicin. Results: Tyrosine phosphorylated ZAP–70 expression was observed in normal lacrimal gland and untreated and chemotherapy treated adenoid cystic carcinoma tissue. Histologically, immunostaining was seen in human lacrimal gland ductal and acinar epithelium. Adenoid cystic carcinoma, the most common non–lymphoid malignant tumor of the lacrimal gland, also expressed activated ZAP–70. Conclusions: ZAP–70 is mainly believed to be a lymphoid protein tyrosine kinase expressed in T and NK cells. ZAP–70 is critically important for lymphocyte activation through cell surface signaling of the TCR/CD3 complex. Murine studies of ZAP–70 mRNA expression demonstrate expression in embryonic thymus, spleen, brain, bronchial epithelia of lung, hemopoietic cells of the liver, and lining epithelia of the intestine. Interestingly, embryonic expression of ZAP–70 in lung, liver, and intestine tissue disappears in newborn and adult mice and persists only in lymphoid and brain tissues. This is the first report of ZAP–70 expression in human non–lymphoid ocular tissue. Moreover, lacrimal gland tissue expresses the activated, phosphorylated form of ZAP–70, suggesting intracellular signaling is occurring. ZAP–70, a PTK critical for lymphocyte signaling, may be important for lacrimal gland function.

Keywords: orbit • lacrimal gland • immunohistochemistry