Limits...
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.

Show MeSH

Related in: MedlinePlus

Chemotactic response of leukocytes to recombinant murine MCP-5. Human peripheral blood mononuclear cells (A), mouse eosinophils  (B), and mouse neutrophils (C) were exposed to increasing concentrations of the indicated chemokines in a modified Boyden chamber, and the number  of cells that migrated through the membrane was determined. Data are the number of cells/×400 field. The results shown are representative experiments  (n = 9 PBMC, n = 7 eosinophils, and n = 3 neutrophils) and presented as the mean ± standard error of eight fields counted of replicate wells.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196097&req=5

Figure 2: Chemotactic response of leukocytes to recombinant murine MCP-5. Human peripheral blood mononuclear cells (A), mouse eosinophils (B), and mouse neutrophils (C) were exposed to increasing concentrations of the indicated chemokines in a modified Boyden chamber, and the number of cells that migrated through the membrane was determined. Data are the number of cells/×400 field. The results shown are representative experiments (n = 9 PBMC, n = 7 eosinophils, and n = 3 neutrophils) and presented as the mean ± standard error of eight fields counted of replicate wells.

Mentions: The chemotactic activity of purified recombinant MCP-5 was evaluated on human peripheral blood monocytes, mouse eosinophils, and mouse neutrophils (Fig. 2). MCP-5 was a potent chemoattractant for human peripheral blood monocytes, as was mouse JE and human MCP-1 (Fig. 2 A). MCP-5 had minimal activity on murine eosinophils and only at doses ⩾1,000 ng/ml. These cells were very responsive to the positive controls eotaxin and MIP-1α (peak chemotaxis at 50 ng/ml or 5 nM), and only minimally responsive to the negative controls JE and MIP-1β (Fig. 2 B). Murine neutrophils exhibited no response to MCP-5, but had a strong response to the controls mouse KC and human IL-8 (Fig. 2 C). These results demonstrate that purified MCP-5 was a potent, dose-dependent, chemotactic agent for peripheral blood monocytes.


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)

Chemotactic response of leukocytes to recombinant murine MCP-5. Human peripheral blood mononuclear cells (A), mouse eosinophils  (B), and mouse neutrophils (C) were exposed to increasing concentrations of the indicated chemokines in a modified Boyden chamber, and the number  of cells that migrated through the membrane was determined. Data are the number of cells/×400 field. The results shown are representative experiments  (n = 9 PBMC, n = 7 eosinophils, and n = 3 neutrophils) and presented as the mean ± standard error of eight fields counted of replicate wells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196097&req=5

Figure 2: Chemotactic response of leukocytes to recombinant murine MCP-5. Human peripheral blood mononuclear cells (A), mouse eosinophils (B), and mouse neutrophils (C) were exposed to increasing concentrations of the indicated chemokines in a modified Boyden chamber, and the number of cells that migrated through the membrane was determined. Data are the number of cells/×400 field. The results shown are representative experiments (n = 9 PBMC, n = 7 eosinophils, and n = 3 neutrophils) and presented as the mean ± standard error of eight fields counted of replicate wells.
Mentions: The chemotactic activity of purified recombinant MCP-5 was evaluated on human peripheral blood monocytes, mouse eosinophils, and mouse neutrophils (Fig. 2). MCP-5 was a potent chemoattractant for human peripheral blood monocytes, as was mouse JE and human MCP-1 (Fig. 2 A). MCP-5 had minimal activity on murine eosinophils and only at doses ⩾1,000 ng/ml. These cells were very responsive to the positive controls eotaxin and MIP-1α (peak chemotaxis at 50 ng/ml or 5 nM), and only minimally responsive to the negative controls JE and MIP-1β (Fig. 2 B). Murine neutrophils exhibited no response to MCP-5, but had a strong response to the controls mouse KC and human IL-8 (Fig. 2 C). These results demonstrate that purified MCP-5 was a potent, dose-dependent, chemotactic agent for peripheral blood monocytes.

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