The alveolar macrophage (AM) is the sentinel phagocytic cell of the lung, performing essential antimicrobial, immunobiologic, and secretory functions within the alveolar units. Like other phagocytes, the AM is capable of generating reactive oxygen metabolites in response to phagocytic or soluble stimuli; this mechanism has been implicated as a mediator of acute lung injury in a variety of disorders. The elucidation of the mechanism by which the human AM mounts the respiratory burst is crucial in the understanding of both its normal microbicidal function and the pathogenesis of its mediation of acute lung injury. The extrapolation from precursor circulating human monocytes or comparison with animal AM's does not define the specific characteristics of initiating mechanisms, oxidative enzymology or stoichiometry of reactive oxygen-derived species found in the stimulated human AM parameters crucial for definition of AM-mediated damage. We endeavor to study 1) the mechanisms of activation of AM respiratory burst and the AM's specific stimulus response coupling, 2) the enzymatic apparatus responsible for the elaboration of toxic products of the burst by isolating constituent components and mechanistic studies, and 3) the character and quantity of a variety of reactive moieties initiated by the generation of superoxide or peroxide in the respiratory burst. The parallel yet important differences in oxidative activities already noted between human phagocytes suggest that such studies are appropriate and methodologically reasonable in deciphering the role the AM in lung injury.
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