LFA-1, AND NOT MAC-1, IS CRUCIAL FOR THE DEVELOPMENT OF HYPERREACTIVITY IN A MURINE MODEL OF NONALLERGIC ASTHMA

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 wi th dinitrofluorobenzene (DNFB) followed by an intranasal challenge wit h the same hapten. Twenty-four hours after the challenge, tracheal hyp erreactivity, a decrease in T cells in the blood, and increased neutro phil numbers in bronchoalveolar lavage fluid (BALF) and blood were obs erved. Monoclonal antibodies (mAbs) directed against the alpha-chains of LFA-1 (FD441.8) and Mac-1 (M1/70) were injected intravenously 2 h b efore and 2 h after the challenge. Treatment with anti-LFA-1 mAb total ly 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 als o evident 24 h after the challenge, was totally inhibited by treatment with anti-LFA-1, whereas anti-Mac-1 had little effect. The increase i n 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 pres ented in this report highlights the possible importance of the adhesio n molecule LFA-1 in the development of tracheal hyperreactivity. Our r esults suggest that LFA-1 present on T cells may play an integral role in this response.