Mechanism for the inflammatory response in primate lungs. Demonstration and partial characterization of an alveolar macrophage-derived chemotactic factor with preferential activity for polymorphonuclear leukocytes.

Neutrophil accumulation in the lung in alpha 1-antitrypsin deficiency. Spontaneous release of leukotriene B4 by alveolar macrophages.

“…Neutrophils are present in the lungs of normal individuals in small numbers. A variety of mediators have been identified which likely play a role in neutrophil recruitment into the lungs, including bacterial endotoxin, complement fragments, platelet-activating factor, interleukin-8, the bacterial equivalent of formyl-methionyl-leucyl-phenylalanine, other arachidonic acid metabolites, and one or more polypeptides (13,(16)(17)(18)(19)(34)(35)(36)(37)(38)(39)(40)(41). The central role of the alveolar macrophage as a mediator of neutrophil accumulation has been clearly documented (42)(43)(44).…”

“…On the basis of these observations, the present study is directed at evaluating the hypothesis that neutrophils accumulate in the alveolar structures of these individuals at least in part because they are attracted by chemotactic signals released by alveolar macrophages. This hypothesis is based on three concepts, including: (a) alveolar macrophages are capable, when activated by surface stimuli, of releasing chemotactic mediators for neutrophils (13)(14)(15)(16)(17)(18)(19); (b) alveolar macrophages have surface receptors for neutrophil elastase (20)(21)(22); and (c) individuals with a I AT deficiency have insufficient alAT in the lower respiratory tract to inhibit the burden ofNE in the local milieu and thus likely have free NE in the alveolar structures (7,23). Putting these concepts together, they lead to a scenario of amplification of normal inflammatory processes, in which free NE resulting from insufficient a 1 AT binds to the NE receptors in alveolar macrophages, causing the macrophages to release mediators with neutrophil chemotactic activity, thus causing an increased number of neutrophils to accumulate in the alveolar structures.…”

Alterations in Macrophage Functions by Environmental Chemicals

“…Although the mechanism for this influx of PMN is not known, there is evidence that the macrophages can secrete a low molecular weight chemotactic factor that preferentially attracts PMN (22, 84). This factor can be isolated from bronchopulmonary lavage fluid (85). It appears that this response is chemical-specific since inhalation of particles of carbon (79), barium sulfate (79), Mn3O4 (55), NiCl2 (35), fly ash (86), chrysotile (59) and silica (79) did not recruit leukocytes at the concentrations tested.…”

Increased expression of the interleukin-8 gene by alveolar macrophages in idiopathic pulmonary fibrosis. A potential mechanism for the recruitment and activation of neutrophils in lung fibrosis.

“…Macrophages from patients with IPF spontaneously release a chemotactic factor for neutrophils (11). This activity has been discriminated into a 400-600-D lipid-containing compound (1 1), and a 5-10-kD protein (14,15). On the basis of similar biological activities and physicochemical properties, it has been suggested (16) that this latter protein may be interleukin 8 (IL-8), a recently purified (17), sequenced (18), and cloned ( 19) monocyte-derived neutrophil chemotactic and granule-releasing factor of molecular mass 8,400 D (16,20).…”