Immunolabeling of gamma-glutamyl transferase 5 in normal human tissues reveals that expression and localization differ from gamma-glutamyl transferase 1

Abstract

Gamma-glutamyl transferase (GGT5) was discovered due to its ability to convert leukotriene C4 (LTC4, a glutathione S-conjugate) to LTD4 and may have an important role in the immune system. However, it was not known which cells express the enzyme in humans. We have developed a sensitive and specific antibody that can be used to detect human GGT5 on western blots and in fixed tissue sections. We localized GGT5 expression in normal human tissues. We observed GGT5 expressed by macrophages present in many tissues, including tissue-fixed macrophages such as Kupffer cells in the liver and dust cells in the lung. GGT5 was expressed in some of the same tissues that have been shown to express gamma-glutamyl transferase (GGT1), the only other enzymatically active protein in this family. But, the two enzymes were often expressed by different cell types within the tissue. For example, GGT5 was expressed by the interstitial cells of the kidney; whereas, GGT1 is expressed on the apical surface of the renal proximal tubules. Other tissues with GGT5-positive cells included: adrenal gland, salivary gland, pituitary, thymus, spleen, liver, bone marrow, small intestine, stomach, testis, prostate and placenta. GGT5 and GGT1 are cell surface enzymes. The different pattern of expression results in their access to different extracellular fluids and therefore different substrates. GGT5 has access to substrates in blood and intercellular fluids, while GGT1 has access primarily to fluids in ducts and glands throughout the body. These data provide new insights into the different functions of these two related enzymes.

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

“…At the same time, LTD 4 was formed in long-term incubations of MM6 cells, in agreement with these cells (Fig. 7), as human macrophages (19), expressing GGT5. However, in previous experiments with lung tissue, induced formation of CysLT including LTD 4 was quick (10-15 min) [see (49)], suggesting involvement of GGT1.…”

“…However, human GGT5 was less efficient compared with human GGT1 regarding formation of LTD 4 in vitro (9). Recently, GGT5 was found in macrophages present in human tissues, most abundant in the lung (19).…”

Proximal Tubule β2-Adrenergic Receptor Mediates Formoterol-Induced Recovery of Mitochondrial and Renal Function after Ischemia-Reperfusion Injury

“…The gGT1 promoter has been used by several groups to generate proximal tubule-specific deletions of target genes (Iwano et al, 2002;Chen et al, 2012;Inoue et al, 2012;Tiwari et al, 2013;Han et al, 2016;Zhou et al, 2018). Although gGT1 can also be expressed in hepatocytes, it is expressed in much higher levels in proximal tubule cells (Hanigan et al, 2015), and gGT-Cre mice primarily express Cre in the kidney (Iwano et al, 2002). Further work showed that gGT-Cre deletes floxed genes in only proximal tubule cells (Chen et al, 2012;Inoue et al, 2012;Tiwari et al, 2013;Han et al, 2016).…”

“…Different letters denote P , 0.05, Two-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) test. types (Hanigan et al, 2015), particularly in pathologic states such as polycystic kidney disease (Starremans et al, 2008) and epithelial-mesenchymal transition (Inoue et al, 2010), the gGT-Cre mouse generates a proximal tubule-specific deletion of floxed genes without any Cre-dependent effects on renal function.…”

Identification of differential gene expression profile from peripheral blood cells of military pilots with hypertension by RNA sequencing analysis

“…But GGT5 gene knockout mice were unable to metabolize LTC4 , resulting in diminished potential of neutrophils infiltrating into the peritoneum. The expression and function of GGT5 in human are rarely reported [ 22 ]. PTGS2 (also known as COX-2 ) could promote carcinogenesis and metastasis of multiple types of tumors.…”