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

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.

CCL2 recruitment of IL‐6‐producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17‐dependent B cell‐mediated autoimmunity

“…The involvement of CCL2 in several experimental models of inflammation and autoimmunity is well established, and appears to partly depend on the ability of this chemokine to direct the inflammatory influx to target organs and to promote Th1 and/or Th2 cells [10][11][12][13]. The autoimmune model of EAMG differs from the other systems studied for at least two reasons.…”

“…The CC chemokine ligand 2 (CCL2), initially known as monocyte chemoattractant protein 1 (MCP-1), is expressed by inflammatory cells at sites of tissue injury [10][11][12][13]. CCL2 directs the migration of monocytes, dendritic cells, NK cells and T cells, and coordinates inflammatory responses during infection [13].…”

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

“…An impact of MCP-1 in this context is very likely [20,47]. The effect of repetitive treatment of mice with mAb RB6-8C5 on the control of intratracheal BCG infection has been recently described [48].…”

“…Expression of several chemokines is up-regulated upon M. tuberculosis infection, but a correlation with anti-tuberculous protection has been difficult to establish [14][15][16][17][18][19][20][21]. Thus far, a significant loss of resistance was only observed in CCR2 -/-mice [22,23].…”

Interleukin‐18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways

“…Levels of the CC chemokine MCP-1/CCL2 are elevated in RA synovial fluid compared with OA synovial fluid (15). Monocyte recruitment and cytokine expression are impaired in MCP-1/CCL2-deficient mice, providing evidence of the role of MCP-1/CCL2 in RA pathogenesis (17). MCP-1/CCL2 attracts memory T lymphocytes and natural killer cells, which have a major function in RA (18).…”