Interactions between alveolar macrophage subpopulations modulate their migratory function

Abstract

To better understand the mechanisms by which alveolar macrophages (AM) are attracted to local sites in the lung, the locomotion of AM in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was investigated. Total bronchoalveolar cells (99% AM) obtained by a nondiscriminating bronchoalveolar lavage procedure migrated toward FMLP over a range of concentrations of 10(-12) M to 10(-6) M. Dose-response experiments showed a biphasic response with two peaks of migration obtained respectively at 5 x 10(-10) M and 10(-8) M. Analysis in the presence and absence of a positive gradient of FMLP revealed that the first peak of migration (5 x 10(-10) M FMLP) corresponded predominantly to chemotactic activity whereas the second peak of migration (10(-8) M FMLP) was associated with chemokinetic activity. To further evaluate these activities of oriented (chemotaxis) vs. random (chemokinesis) migration, AM were separated into two fractions by a two-step bronchoalveolar lavage procedure. Whereas fraction 1 displayed exclusively chemokinesis in response to higher concentrations of FMLP (10(-8) M), fraction 2 was totally unresponsive to FMLP over a wide range of concentrations (5 x 10(-11) M - 10(-7) M). When both fractions were combined, however, the chemotactic response to low concentrations of FMLP (5 x 10(-10) M) was restored. Additional analysis of these two AM fractions indicated that fraction 1 AM had a significantly lower degree of adherence and aggregation than fraction 2 AM. These data suggest that cell-cell cooperation is important for AM chemotactic response to FMLP and that such interaction may involve changes in adherence and aggregation.