Abnormalities in Monocyte Recruitment and Cytokine Expression in Monocyte Chemoattractant Protein 1–deficient Mice

TLDR

Monocyte chemoattractant protein 1 (MCP‑1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and NK cells, but it is unclear whether MCP‑1 has a unique in vivo role because other chemokines share target cells and its receptor CCR2 binds additional ligands. The study aimed to determine whether MCP‑1 uniquely recruits mononuclear cells by disrupting the SCYA2 gene and testing MCP‑1–deficient mice in inflammatory models. MCP‑1–deficient mice were generated by SCYA2 disruption and evaluated in models of thioglycollate‑induced peritonitis, delayed‑type hypersensitivity, Schistosoma‑induced granuloma formation, and Mycobacterium tuberculosis infection. MCP‑1–deficient mice exhibited specific failures to recruit monocytes after thioglycollate, impaired monocyte accumulation in DTH lesions, reduced pulmonary granuloma development and cytokine expression in Schistosoma infection, yet cleared M.

Abstract

Monocyte chemoattractant protein 1 (MCP-1) is a CC chemokine that attracts monocytes, memory T lymphocytes, and natural killer cells. Because other chemokines have similar target cell specificities and because CCR2, a cloned MCP-1 receptor, binds other ligands, it has been uncertain whether MCP-1 plays a unique role in recruiting mononuclear cells in vivo. To address this question, we disrupted SCYA2 (the gene encoding MCP-1) and tested MCP-1–deficient mice in models of inflammation. Despite normal numbers of circulating leukocytes and resident macrophages, MCP-1−/− mice were specifically unable to recruit monocytes 72 h after intraperitoneal thioglycollate administration. Similarly, accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions was impaired, although the swelling response was normal. Development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs was blunted in MCP-1−/− mice, as was expression of IL-4, IL-5, and interferon γ in splenocytes. In contrast, MCP-1−/− mice were indistinguishable from wild-type mice in their ability to clear Mycobacterium tuberculosis. Our data indicate that MCP-1 is uniquely essential for monocyte recruitment in several inflammatory models in vivo and influences expression of cytokines related to T helper responses.