Expression of the chemokines, monocyte chemotactic protein (MCP)-1 and MCP-2 in endometrium of normal women and Norplant® users, does not support a central role in macrophage infiltration into endometrium

Abstract

The endometrium contains many leukocytes, including macrophages, the numbers varying with the time of the menstrual cycle and being maximal peri-menstrually. The long-acting progestogenic contraceptive Norplant®, has a high rate of discontinuation due to uterine bleeding; this is associated with large numbers of endometrial macrophages. Monocyte chemotactic proteins (MCP) act to recruit and activate monocytes into sites of inflammation. This study compared the cellular localization of endometrial MCP-1 and MCP-2 across the normal menstrual cycle and in users of Norplant®. Both MCP-1 and MCP-2 were present in normal endometrium, but with very different patterns of cellular location and considerable variability between individuals. MCP-1 of epithelial origin was present in 77% of tissues, while stromal staining was present in 52% and vascular staining in 34% of samples. MCP-1 was also released from both epithelial and stromal cells in culture. MCP-2 staining was predominantly epithelial and was found in 52% of tissues while stromal staining was present in only 3/56 samples. Vascular staining of MCP-2 was found in 2/56 samples. The epithelial staining was mostly punctate and sometimes within uterine secretions. No correlation of staining for MCP-1 or -2 with the phase of the cycle was found in any cellular compartment. Very little immunoreactive MCP-1 or MCP-2 was detected in endometrium from Norplant® users regardless of morphological subtype. These distributions do not support a role for either MCP-1 or MCP-2 in the migration of macrophages into the endometrium and suggest that these cytokines may have other functions in this tissue.