Chromogranin A immunoreactivity and Grimelius' argyrophilia

Various endocrine cells can be stained by the argyrophil reaction of Grimelius. This silver stain has recently been attributed to chromogranin A, an acidic glycoprotein, that is present in many endocrine cells. Using serial sections of plastic-embedded tissues (adrenal medulla, pancreas, gastric mucosa) various endocrine cells were investigated for their content of chromogranin A immunoreactivity and for their argyrophilia. The findings in four species (man, cattle, pig, guinea pig) showed that chromogranin A immunoreactivity and argyrophil stain partly overlap in identical endocrine cells, but do not necessarily coincide in the majority of endocrine cells. We found that endocrine cells could be positive for chromogranin A and argyrophilia (e.g., aminergic endocrine cells); or positive for chromogranin A but negative for argyrophilia (e.g., insulin cells of all species; somatostatin cells of cattle and pig); or negative for chromogranin A but positive for argyrophilia (e.g., glucagon cells of pig and guinea pig); or negative for chromogranin A and argyrophilia (e.g., somatostatin cells of man and guinea pig). Such heterogeneities of the staining pattern for chromogranin A and argyrophil silver reaction were also observed in individual endocrine cells of a given population (e.g., gastrin cells). Hence, although recent dot-blot tests have shown that chromogranin A is an argyrophilic substance, in tissue sections chromogranin A immunostaining and Grimelius' silver staining did not coincide in various endocrine cells, for unknown reasons. Therefore, it is recommended to use both chromogranin A immunohistochemistry and the classical Grimelius' silver stain to "mark" that vast majority of endocrine cells in tissue sections.