Am. J. Respir. Crit. Care Med., Vol 153, No. 2, Feb 1996, 521-529.
LFA-1, and not Mac-1, is crucial for the development of hyperreactivity in a murine model of nonallergic asthma
PG Bloemen, TL Buckley, MC van den Tweel, PA Henricks, FA Redegeld, AS Koster and FP Nijkamp
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, The Netherlands.
In this study, we investigated the importance of the beta 2-integrins for
the development of tracheal hyperreactivity in a murine model for
nonallergic asthma. The response was induced by skin sensitization with
dinitrofluorobenzene (DNFB) followed by an intranasal challenge with the
same hapten. Twenty-four hours after the challenge, tracheal
hyperreactivity, a decrease in T cells in the blood, and increased
neutrophil numbers in bronchoalveolar lavage fluid (BALF) and blood were
observed. Monoclonal antibodies (mAbs) directed against the alpha- chains
of LFA-1 (FD441.8) and Mac-1 (M1/70) were injected intravenously 2 h before
and 2 h after the challenge. Treatment with anti-LFA-1 mAb totally
inhibited the development of tracheal hyperreactivity measured 24 h after
the challenge, whereas anti-Mac-1 mAb had only a partial effect on this
response. The decrease in T cells in the blood, which was also evident 24 h
after the challenge, was totally inhibited by treatment with anti-LFA-1,
whereas anti-Mac-1 had little effect. The increase in the number of
neutrophils in BALF at this time point was completely inhibited by both
anti-LFA-1 and anti-Mac-1. In summary, evidence presented in this report
highlights the possible importance of the adhesion molecule LFA-1 in the
development of tracheal hyperreactivity. Our results suggest that LFA-1
present on T cells may play an integral role in this response.
