Histochemical changes in the composition of mucins in goblet cells during methotrexate-induced mucosal atrophy in rats.

Changes in the composition of mucins in jejunal goblet cells were investigated histochemically after a single intraperitoneal injection of methotrexate in rats (40 mg methotrexate/kg body weight). At 48 h after injection of methotrexate, when mitotic activity in the crypts approximates to zero, an almost complete disappearance of mucin-containing goblet cells can be observed. At 96h, when proliferative activity in crypts is excessive, neutral mucin- and sialomucin-containing goblet cells dominate in the crypts, whereas in controls the crypts display sulphomucin-containing goblet cells. At 144h neutral mucin- and sulphomucin-containing goblet cells dominate in the crypts. Both at 48 and 96h after injection of methotrexate a significant decrease in the number of villous goblet cells takes place, whereas with respect to the quality of the mucins in the goblet cells no difference can be found in comparison with control rats. At 144h the villi have recovered from the preceding temporary decrease of goblet cells. The histochemical composition of the population of goblet cells is still aberrant and shows goblet cells containing neutral mucins and sulphomucins principally, whereas in controls sialomucin-containing goblet cells dominate on the villi. The established changes in the composition of mucins in goblet cells cannot be attributed to methotrexate-induced malnutrition, as pair-fed control rats clearly demonstrate. Our results clearly demonstrate that conspicuous quantitative as well as qualitative changes in the synthesis of mucins in goblet cells occur during the hyporegenerative and hyperregenerative phase of methotrexate-induced mucosal atrophy.