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Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1.

Sarafi MN, Garcia-Zepeda EA, MacLean JA, Charo IF, Luster AD - J. Exp. Med. (1997)

Bottom Line: Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes.MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5.These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

View Article: PubMed Central - PubMed

Affiliation: Infectious Disease Unit, Massachusetts General Hospital, Boston, USA.

ABSTRACT
The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

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MCP-5 mRNA expression in murine models of pulmonary  inflammation. Northern analysis of total RNA isolated from the lungs of  nonimmunized nonchallenged mice (NN), sham-immunized mice challenged with aerosolized OVA (SC), OVA-immunized mice challenged  with aerosolized OVA (IC), or from the lungs of mice at 7, 10, and 14 d  after infection with Nb. All OVA challenged tissue was harvested at 3 h  (n = 3). Each lane represents an individual mouse. Blots were hybridized  sequentially with MCP-5, JE, and rpL32 cDNA probes and exposed for  14 d, 3 d, and 18 h, respectively.
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Figure 8: MCP-5 mRNA expression in murine models of pulmonary inflammation. Northern analysis of total RNA isolated from the lungs of nonimmunized nonchallenged mice (NN), sham-immunized mice challenged with aerosolized OVA (SC), OVA-immunized mice challenged with aerosolized OVA (IC), or from the lungs of mice at 7, 10, and 14 d after infection with Nb. All OVA challenged tissue was harvested at 3 h (n = 3). Each lane represents an individual mouse. Blots were hybridized sequentially with MCP-5, JE, and rpL32 cDNA probes and exposed for 14 d, 3 d, and 18 h, respectively.

Mentions: To examine the regulation of MCP-5 during in vivo immune responses, we examined its expression in the lungs of mice following infection with Nb and in a murine model of OVA-induced pulmonary inflammation (Fig. 8). Following infection with Nb, MCP-5 lung mRNA levels were markedly increased by day 7, peaked by day 10, and returned to baseline by day 14. The kinetics of MCP-5 mRNA accumulation preceded the peak recruitment of pulmonary macrophages, neutrophils, and eosinophils that characterize the granulomatous immune response to this nematode pathogen (23). MCP-5 mRNA was also detected in OVA-immunized mice 3 h after aerosol challenge (Fig. 8), and remained elevated at 48 h (data not shown). MCP-5 mRNA remained at prechallenge levels in challenged sham-immunized mice (Fig. 8). Again, the kinetics of MCP-5 mRNA accumulation preceded the peak accumulation of pulmonary macrophages, lymphocytes, and eosinophils that characterize the immune response in this model (22). Like MCP-5, JE was induced in both murine models of pulmonary inflammation; however, in the OVA model, levels of JE mRNA returned to baseline by 48 h, while MCP-5 levels remained elevated (data not shown).


Murine monocyte chemoattractant protein (MCP)-5: a novel CC chemokine that is a structural and functional homologue of human MCP-1.

Sarafi MN, Garcia-Zepeda EA, MacLean JA, Charo IF, Luster AD - J. Exp. Med. (1997)

MCP-5 mRNA expression in murine models of pulmonary  inflammation. Northern analysis of total RNA isolated from the lungs of  nonimmunized nonchallenged mice (NN), sham-immunized mice challenged with aerosolized OVA (SC), OVA-immunized mice challenged  with aerosolized OVA (IC), or from the lungs of mice at 7, 10, and 14 d  after infection with Nb. All OVA challenged tissue was harvested at 3 h  (n = 3). Each lane represents an individual mouse. Blots were hybridized  sequentially with MCP-5, JE, and rpL32 cDNA probes and exposed for  14 d, 3 d, and 18 h, respectively.
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Related In: Results  -  Collection

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Figure 8: MCP-5 mRNA expression in murine models of pulmonary inflammation. Northern analysis of total RNA isolated from the lungs of nonimmunized nonchallenged mice (NN), sham-immunized mice challenged with aerosolized OVA (SC), OVA-immunized mice challenged with aerosolized OVA (IC), or from the lungs of mice at 7, 10, and 14 d after infection with Nb. All OVA challenged tissue was harvested at 3 h (n = 3). Each lane represents an individual mouse. Blots were hybridized sequentially with MCP-5, JE, and rpL32 cDNA probes and exposed for 14 d, 3 d, and 18 h, respectively.
Mentions: To examine the regulation of MCP-5 during in vivo immune responses, we examined its expression in the lungs of mice following infection with Nb and in a murine model of OVA-induced pulmonary inflammation (Fig. 8). Following infection with Nb, MCP-5 lung mRNA levels were markedly increased by day 7, peaked by day 10, and returned to baseline by day 14. The kinetics of MCP-5 mRNA accumulation preceded the peak recruitment of pulmonary macrophages, neutrophils, and eosinophils that characterize the granulomatous immune response to this nematode pathogen (23). MCP-5 mRNA was also detected in OVA-immunized mice 3 h after aerosol challenge (Fig. 8), and remained elevated at 48 h (data not shown). MCP-5 mRNA remained at prechallenge levels in challenged sham-immunized mice (Fig. 8). Again, the kinetics of MCP-5 mRNA accumulation preceded the peak accumulation of pulmonary macrophages, lymphocytes, and eosinophils that characterize the immune response in this model (22). Like MCP-5, JE was induced in both murine models of pulmonary inflammation; however, in the OVA model, levels of JE mRNA returned to baseline by 48 h, while MCP-5 levels remained elevated (data not shown).

Bottom Line: Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes.MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5.These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

View Article: PubMed Central - PubMed

Affiliation: Infectious Disease Unit, Massachusetts General Hospital, Boston, USA.

ABSTRACT
The chemokines are a large family of cytokines that control the recruitment of leukocytes in immune and inflammatory responses. We describe the isolation of a novel murine CC chemokine that, based on its biological and structural features, we have named monocyte chemoattractant protein (MCP)-5. MCP-5 mapped to the CC chemokine cluster on mouse chromosome 11 and was most closely related to human MCP-1 in structure (66% amino acid identity). Purified recombinant MCP-5 protein was a potent chemoattractant for peripheral blood monocytes, was only weakly active on eosinophils at high doses, and was inactive on neutrophils. MCP-5 induced a calcium flux in peripheral blood mononuclear cells, but not in purified murine eosinophils or neutrophils. Consistent with these results, MCP-5 induced a calcium flux in human embryonic kidney (HEK)-293 cells transfected with human and murine CCR2, a CC chemokine receptor expressed on monocytes. MCP-5 did not induce a calcium flux in HEK-293 cells transfected with CCR1, CCR3, or CCR5. Constitutive expression of MCP-5 mRNA was detected predominantly in lymph nodes, and its expression was markedly induced in macrophages activated in vitro and in vivo. Moreover, MCP-5 expression was up-regulated in the lungs of mice following aerosolized antigen challenge of sensitized mice, and during the host response to infection with Nippostrongylus brasiliensis. These data indicate that MCP-5 is a novel and potent monocyte active chemokine that is involved in allergic inflammation and the host response to pathogens.

Show MeSH
Related in: MedlinePlus