Formyl-methionyl-leucyl-phenylalanine causes bronchoconstriction in rabbits

Abstract

Formyl-methionyl-leucyl-phenylalanine (FMLP) is a synthetic acylated oligopeptide related to chemotactic peptides released by bacteria. In order to determine whether FMLP causes bronchoconstriction in vivo, we studied the effects of nebulized FMLP on lung resistance (RL) in the rabbit. In fourteen rabbits baseline RL was measured and than dimethylsulfoxide (DMSO) alone and 0.3, 1, 3 and 10 mg/ml FMLP in DMSO was nebulized and inhaled by the rabbits over periods of 2 min each. After each concentration the RL was re-measured and the results expressed as a % of the RL following DMSO alone. In 6 rabbits the response to serial nebulization of DMSO alone was 5.5 +/- 10.4% (mean +/- 2 SD). In 8 rabbits receiving FMLP there was a dose dependent increase in RL of 20% or greater whereas 6 rabbits failed to respond. Since there are known receptors for FMLP on neutrophils, 10 further rabbits were rendered neutropenic using nitrogen mustard and then studied as above. Eight of these rabbits failed to respond significantly to FMLP whereas 2 had a 20% or greater increase in RL. In each bronchial specimen from 6 additional rabbits FMLP failed to induce airway contraction in vitro. We conclude that FMLP causes a variable degree of bronchoconstriction in rabbits, that this response may, in part, be mediated via the neutrophil and is unlikely to be due to direct smooth muscle contraction.