Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo.
We have previously reported that monocyte chemoattractant protein-1 (MCP-1) is the most potent histamine-releasing factor (HRF) for basophils. Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has modest histamine-releasing activity. The objective of this study was to investigate whether MCP-1 and MIP-1 alpha would activate mast cells in vivo and induce a cutaneous inflammatory reaction in mice. To this goal, mouse hind footpads were separately injected with 20 microliters of human recombinant MCP-1 or MIP-1 alpha (10(-7) M). Diluent was used as a control in the second footpad. The footpad-swelling response was measured at 30 min, 1 h, and then hourly for 6 h. Both MCP-1 (2.72 +/- 0.2 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) and MIP-1 alpha (3.0 +/- 0.1 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) induced an immediate swelling reaction. The immediate reaction was followed by a sustained late reaction that peaked within 1 h and lasted for more than 6 h. Histologic examination of the footpads, obtained at hour 2, revealed that MCP-1 caused mild mononuclear cell infiltrates, moderate degranulation of mast cells, and soft tissue swelling. In contrast, MIP-1 alpha induced a severe inflammatory reaction that consisted of neutrophils, mononuclear cells, and degranulated mast cells. Electron microscope examination of the tissue revealed features of extensive mast cell degranulation by MIP-1 alpha and to a lesser extent by MCP-1. Thus, we conclude that mast cells are activated on injection of MCP-1, whereas degranulation of mast cells and recruitment of leukocytes contribute to the footpad reaction induced with MIP-1 alpha.
Alam
R
R
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0762.
Kumar
D
D
Anderson-Walters
D
D
Forsythe
P A
PA
D000818:Animals; D015550:Cell Degranulation; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D002630:Chemotactic Factors / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D016207:Cytokines / Q000276:immunology*; D007111:Immunity, Cellular; D019402:Macrophage Inflammatory Proteins; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D015846:Monokines / Q000276:immunology*; D012882:Skin Tests
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D002630:Chemotactic Factors; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines