Mechanism by which cigarette smoke attracts polymorphonuclear leukocytes to lung.

C igarette smoking is a major risk factor in the development of pulmonary emphysema, a chronic disorder thought to be caused by excess protease activity in lung. Although inhalation of cigarette smoke is associated with accumulation of polymorphonuclear leukocytes (PMN; a major source of preformed proteases) in the lung, cigarette smoke, by itself, is not chemotactic for PMN. Since alveolar macrophages (AM) interact with cigarette smoke in vivo and are capable of releasing a chemotactic factor (CF) for PMN, the present study was undertaken to determine if cigarette smoke might stimulate AM to release a CF for PMN. To evaluate this concept, AM obtained by bronchoalveolar lavage (BAL) of five nonsmoking and six cigarette smoking individuals were evaluated for their ability to secrete a CF for PMN either spontaneously or following in vitro exposure to cigarette smoke for three hours. In smokers, AM from each patient spontaneously released CF for PMN (100±15 PMN/hpf) and, as an in vivo correlate, their BAL contained 6 ± 1 percent PMN. In nonsmoking controls, AM did not spontaneously release CF for PMN (5±1 percent PMN/hpf) and their BAL contained <1% PMN. In addition, normal AM could be stimulated to release CF for PMN by exposing them in vitro to cigarette smoke (85±10 PMN/hpf). AM supernatants containing the CF (but free of cigarette smoke) not only attracted PMN, but also activated PMN to release their