GRANULOCYTE-ALVEOLAR-MACROPHAGE INTERACTION IN THE PULMONARY CLEARANCE OF STAPHYLOCOCCUS-AUREUS

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Abstract
A bolus inoculation method for delivery of a large range of inocula to animal lungs was developed; relatively precise inocula were delivered to .apprx. 20% of the lung volume of mice without lung damage by the procedure. The lung clearance of inocula of S. aureus in incremental doses between 105-108 organisms was studied. The phagocytic cell response to the organisms was studied by bronchoalveolar lavage; 105 S. aureus were promptly cleared by alveolar macrophages, as has been the case for a similar number of organisms delivered by an aerosol inoculum. An inoculum of 106 was cleared slowly but completely and elicited a modest granulocyte response; 107 S. aureus evoked a marked granulocyte response, but the number of organisms remained relatively constant for a 12 h observation interval. The highest inoculum of 108 organisms proliferated and killed mice by 12 h, despite an even greater granulocyte response. Most of the bacteria of the smallest inoculum were histologically observed to be associated with alveolar macrophages; for larger inocula, most staphylococci were granulocyte associated. Apparently, the clearance of S. aureus is dose dependent and a dual phagocytic system is necessary for clearance of large inocula. At very high initial depositions, the combined phagocytes are incapable of successful lung defense and pneumonia ensues.