Histamine stimulates alveolar macrophages to release neutrophil and monocyte chemotactic activity

Histamine and serotonin are important inflammatory mediators In the pathoph ysiology of asthma, and asthmatic patients have higher plasma histamine and serotonin levels than non-asthmatic control subjects. Alveolar macrophages (AMs) synthesize and secrete a large number of substances that play a key role In acute and chronic inflammation including asthma. We postulated that AMs might release chemotactic activity for neutrophils and monocytes in re sponse to histamine or serotonin. To test this hypothesis, bovine AMs were cultured, and the supernatant fluids were evaluated for neutrophil chemotac tic activity (NCA) and monocyte chemotactic activity (MCA) by a blind well chamber technique. AMs released chemotactic activity in response to histami ne and serotonin In a close- and time-dependent manner (P < .05). Partial c haracterization and molecular sieve column chromatography revealed that low -molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhi bitors significantly blocked the release of chemotactic activity. Leukotrie ne B-4 receptor antagonists blocked the chemotactic activity. Immunoreactiv e leukotriene B-4 significantly increased in supernatant fluids in response to histamine and serotonin. The receptor responsible for the release of ch emotactic activity in response to histamine was the H-2 receptor. These dat a demonstrate that AMs release NCA and MCA in response to histamine or sero tonin (or both) and may modulate the inflammatory cell recruitment into the lung.