Release of RANTES, MIP-1 α , and MCP-1 into Asthmatic Airways Following Endobronchial Allergen Challenge

Abstract

We have investigated the presence of regulated on activation, normal T-cell expressed and probably secreted (RANTES), macrophage inflammatory peptide-1 alpha (MIP-1 alpha), and macrophage chemotactic peptide (MCP-1) in the bronchoalveolar lavage fluid (BALF) obtained from normal (n = 7) and stable asthmatic subjects (n = 8), and studied their kinetic release into asthmatic airways following endobronchial allergen challenge (n = 18). Measurements of RANTES, MIP-1 alpha, and MCP-1 in 10 times (10x) concentrated BALF showed that these three chemokines were present in both normal controls and stable asthmatic patients, but no significant difference between the two groups was found in the levels of the three chemokines. However, at 4 h after allergen challenge, BALF levels of RANTES, MIP-1 alpha, and MCP-1 were significantly increased in fluid obtained from the allergen-challenge site when compared with the saline-challenge control site (median: 175 pg/ml versus 11.5 pg/ml, 258 pg/ml versus 88 pg/ml, and 900 pg/ml versus 450 pg/ml, respectively). At 24 h, levels of the three chemokines returned to baseline values. To investigate whether cells in BALF obtained 4 h after allergen exposure release chemokines, they were cultured for 24 h. BALF cells from the allergen site released more RANTES and MCP-1 than those from the saline site, but released similar amounts of MIP-1 alpha. These findings suggest that RANTES, MIP-1 alpha, and MCP-1 may regulate cell trafficking in asthma in response to allergen exposure.

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

“…Fc⑀RI-and CCR1-activated RBL-CCR1 Cells-CCL2 plays a critical role in activation and accumulation of leukocytes in allergic inflammatory tissues (3,(7)(8)(9)15). To examine whether cross-talk between Fc⑀RI-and CCR-mediated signaling pathways in mast cells is involved in expression of this chemokine, we used RBL-2H3 cells expressing human CCR1, a model cell line of mucosal type mast cells.…”

“…Some chemokines, such as CCL2/MCP-1 (monocyte chemotactic protein 1), CCL3/MIP-1␣ (macrophage inflammatory protein-1␣), CCL5/RANTES (regulated upon activation, normal T-cell expressed and secreted), and CCL11/eotaxin-1, have been reported to activate mouse, rat, or human mast cells (3)(4)(5)(6). Abundant expression of these CC chemokines and accumulation of leukocytes has also been observed in allergic inflammatory tissues (7)(8)(9). It is very likely that Fc⑀RI and CCR We previously found that CCL3 acts as a co-stimulator for Fc⑀RI-mediated degranulation in conjunctival mast cells using CCL3-deficient mice (10).…”

“…CCL2 is a chemoattractant to induce migration of monocytes, T cells, and eosinophils (3,9). Increased expression of CCL2 protein in inflammatory tissues of allergic patients has been observed (3,(7)(8)(9)15). Targeting chemokine(s) is a strategy to establish new anti-inflammatory drugs for treatment of allergenic diseases.…”

A polymorphism in the CCL2 chemokine gene is associated with asthma risk: a case–control and a family study in Tunisia

“…41 CCL2 mediates airway hyperactivity in normal and allergic mice and directly induces in vitro pulmonary mast cell degranulation. 42 Several human studies demonstrate the upregulation of CCL2 during asthmatic responses, 43,44 and CCL2 protein expression in bronchial tissue is significantly higher in subjects with asthma than in control subjects. 43 In our study, plasma CCL2 protein levels were higher in the case than in the control group.…”

Maximal response plateau to methacholine as a reliable index for reducing inhaled budesonide in moderate asthma

“…The mechanisms by which eosinophils are recruited are complex but appear to involve the elaboration of cytokines such as IL-3, IL-5, and granulocyte-macrophage colonystimulating factor (GM-CSF), as well as the CC-chemokines "regulated on activation, normal T-cells expressed and secreted" (RANTES), monocyte chemoattractant protein (MCP)-3, and MCP-4 [30,31]. In particular, IL-5 selectively promotes eosinophil function [32] and together with IL-3 and GM-CSF, activates eosinophils to release more sulphidopeptide leukotrienes and secrete cationic proteins toxic to the airway epithelium [30].…”