Chromogranin A in the Human Gastrointestinal Tract: An Immunocytochemical Study with Region-specific Antibodies

Abstract

S U M M A R YWe studied the immunoreactivity of 12 different region-specific antibodies to the chromogranin A (CgA) molecule in the various neuroendocrine cell types of the human gastrointestinal (GI) tract by using double immunofluorescence techniques. These staining results were compared with others obtained with a commercial monoclonal CgA antibody (LK2H10). G (gastrin)-cells showed immunoreactivity to virtually all region-specific antibodies, but with varying frequency. Most intestinal EC (enterochromaffin)-and L (enteroglucagon)-cells were immunoreactive to the antibodies to the N-terminal and mid-portion of the CgA molecule, whereas the EC-cells in the stomach reacted with fewer region-specific antibodies. D (somatostatin)-cells reacted to the CgA 411-424 antibody and only occasionally showed immunoreactivity to the other CgA antibodies. A larger cytoplasmic area was stained with the antibodies to than with the other antibodies tested. These differences in staining pattern may reflect different cleavage of the CgA molecule in different cell types and at different regions of the GI tract.

Prognostic value of chromogranin A in severe sepsis: data from the FINNSEPSIS study

“…Production of CgA has also been reported in the myocardium during cardiac disease [10,11], but confirmation of myocardial CgA production in severe sepsis will require a translational investigational program similar to models used to demonstrate myocardial chromogranin production in cardiac disease. Additional sources for CgA release, beyond the adrenergic system and the myocardium, could be the gastrointestinal or the immune system as CgA is produced throughout the gastrointestinal tract [34] and in activated leucocytes [35]. In agreement with some previous studies [11], we also found high CgA levels in patients treated with proton pump inhibitors in the initial phase of severe sepsis.…”

Selective expression of TLQP-21 and other VGF peptides in gastric neuroendocrine cells and modulation by feeding

“…A parallel is often drawn between VGF and the chromograninsecretogranin family of proteins, because of their selective localisation in secretory granules, as well as their role as precursors of multiple bioactive peptides (Helle 2004). Chromogranins, too, are differentially processed in gastric endocrine cells (Watkinson et al 1991, Watkinson & Dockray 1992, Portela-Gomes & Stridsberg 2002), although to a profile different from the one we observed for VGF peptides. In fact, G cells showed immunoreactivity to virtually all region-specific antibodies to chromogranin A (Portela-Gomes & Stridsberg 2002), as opposed to the limited reactivity of VGF peptides we could demonstrate in such cell type.…”

The endocrine role for chromogranin A: A prohormone for peptides with regulatory properties

“…1). There may also be species-, cell-and tissue-specific processing of CgA, as in the rat [26] and in the human gastrointestinal tract [27][28][29].…”

“…In addition, the specific inhibition of cardiac contractility and the counteraction of the b-adrenergic inotropism were most potently elicited by VS-1, CgA 7-57 and CgA 1 -40SS , implicating the disulfidebridged region as a requirement for the marked negative inotropism whether mechanically activated or stimulated by ISO [43]. Interestingly, the least effective inhibitor, the frog CgA 4-16 is more acidic than the bovine homologue, while there is a complete homology between the frog, porcine, bovine and human CgA [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and CgA 40-62 [101]. Hence, the modulation of myocardial contractility in the frog heart by structurally different regions of frog and bovine VS-I is consistent with a functional conservation of this domain.…”