Neutralization of Macrophage Inflammatory Protein 2 (MIP-2) and MIP-1α Attenuates Neutrophil Recruitment in the Central Nervous System during Experimental Bacterial Meningitis

Abstract

Chemokines are low-molecular-weight chemotactic cytokines that have been shown to play a central role in the perivascular transmigration and accumulation of specific subsets of leukocytes at sites of tissue damage. Using in situ hybridization (ISH), we investigated the mRNA induction of macrophage inflammatory protein 2 (MIP-2), MIP-1α, monocyte chemoattractant protein 1 (MCP-1), and RANTES. Challenge of infant rats’ brains with Haemophilus influenzae type b intraperitoneally resulted in the time-dependent expression of MIP-2, MIP-1α, MCP-1, and RANTES, which was maximal 24 to 48 h postinoculation. Immunohistochemistry showed significant increases in neutrophils and macrophages infiltrating the meninges, the ventricular system, and the periventricular area. The kinetics of MIP-2, MIP-1α, MCP-1, and RANTES mRNA expression paralleled those of the recruitment of inflammatory cells and disease severity. Administration of anti-MIP-2 or anti-MIP-1α antibodies (Abs) resulted in significant reduction of neutrophils. Administration of anti-MCP-1 Abs significantly decreased macrophage infiltration. Combined studies of ISH and immunohistochemistry showed that MIP-2- and MIP-1α-positive cells were neutrophils and macrophages. MCP-1-positive cells were neutrophils, macrophages, and astrocytes. Expression of RANTES was localized predominantly to resident astrocytes and microglia. The present study indicates that blocking of MIP-2 or MIP-1α bioactivity in vivo results in decreased neutrophil influx. These data are also the first demonstration that the C-C chemokine MIP-1α is involved in neutrophil recruitment in vivo.

Simvastatin protects against cholestasis‐induced liver injury

“…This observation adds the liver to the list of tissues, such as brain (Stanislaus et al, 2001), heart (Lefer et al, 1999), retina (Honjo et al, 2002), colon (Sasaki et al, 2003), synovium (Yamagata et al, 2007) and lung (Naidu et al, 2003), in which statins have been found to attenuate leukocyte infiltration. Convincing data in the literature have shown that chemokines constitute a dominating group of molecules regulating tissue accumulation of leukocytes in numerous disease models (Feng et al, 1995;Schmal et al, 1996;Diab et al, 1999;Li et al, 2004b). In the present study, we observed not only that BDL markedly increased hepatic formation of MIP-2 and KC but that pre-treatment with simvastatin also abolished cholestasis-induced CXC chemokine production in the liver.…”

TLR2-mediated leukocyte trafficking to the developing brain

“…MIP-1a is known to have a role as a chemoattractant in recruiting monocytes and neutrophils to inflammation sites [35]. CCL3 is also detected in the CSF of individuals with bacterial meningitis [36] and its neutralization in experimental meningitis inhibits neutrophil recruitment to the CNS [37]. Expression of MIP-1a in the CNS could potentially attract cells and might, in part, explain the difference between P3C and LPS in causing infiltration of cells into the brain.…”

The influence of titanium surface characteristics on macrophage phenotype polarization during osseous healing in type I diabetic rats: a pilot study

“…MCP-1 (also known as CCL2) is a major chemokine that induces the recruitment and activation of monocytes, T cells, and NK cells at the early inflammatory phases (Morimoto et al 2006). MIP-2 is another important chemokine in the wound healing stages that attracts mainly polymorphonuclear granulocytes (Diab et al 1999). Down-regulation of these chemokines could therefore play a role in the improved healing seen in response to the modified surface (Schlegel et al 2011;Lee et al 2013).…”