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Am. J. Respir. Crit. Care Med., Volume 156, Number 5, November 1997, 1377-1383

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

STEPHEN T. HOLGATE, KATHLEEN S. BODEY, ALENKA JANEZIC, ANTHONY J. FREW, ALLEN P. KAPLAN, and LUIS M. TERAN

University Medicine, Southampton General Hospital, Southampton, United Kingdom; and Department of Medicine, State University of New York at Stony Brook, New York

We have investigated the presence of regulated on activation, normal T-cell expressed and probably secreted (RANTES), macrophage inflammatory peptide-1alpha (MIP-1alpha ), 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-1alpha , and MCP-1 in 10 times (10×) 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-1alpha , 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-1alpha . These findings suggest that RANTES, MIP-1alpha , and MCP-1 may regulate cell trafficking in asthma in response to allergen exposure.




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