Organ-Specific Disposition of Group B Streptococci in Piglets: Evidence for a Direct Interaction with Target Cells in the Pulmonary Circulation

Abstract

ABSTRACT. Despite the serious pulmonary manifestaintact animal could be initiated by a direct interaction tions of early onset group B streptococcal (GBS) sepsis, it between GBS and resident lung cells without obligatory is not known whether the organism distributes into lung participation by other organ systems. (Pediatr Res 27: tissue and whether adverse pulmonary hemodynamic ab-344-348,1990) normalities relate to an interaction between the organism and target cells in the pulmonary vascular bed. AccordAbbreviations ingly, this study evaluated the distribution and fate of GBS in the lung, liver, and spleen of anesthetized infant piglets GBS, group B streptococcus and in isolated, salt solution-perfused piglet lung prepara-HBSS, Hanks' balanced salt solution tions. GBS were radiolabeled with lllIndium-oxine and cfu, colony-forming unit infused at a dose of 108 organisms/kg/min for 15 min into Ppa, pulmonary arterial pressure anesthetized piglets ranging in age from 5-10 d. Forty-five Pla, left atrial pressure min after termination of the infusion, animals were killed Rt, total resistance and specimens of lung, liver, spleen, and blood were excised Ra, arterial resistance and the relative deposition and viability of GBS were Rv, venous resistance determined. Most of the recovered bacteria were detected Pdo, double occlusion pressure in the lung (53.2 f 3.9%) followed by the liver (41.4 f 2.0%) and spleen (2.2 f 0.38%). GBS detected in the blood was estimated to be only 3.2 2 1.0% of the infused dose. Viability of GBS was least in the lung (21.4 2 2.6%)The question is straight-forward: Does GBS promote pulmorelative to the liver (45.7 f 11.2%) and spleen (83.4 +: nary hypertension in the newborn through interaction with a 19.5%). After a 60-min GBS infusion, transmission elec-target cell in the lung? The concept that GBS-induced pulmonary tron microscopy localized the organism within pulmonary hypertension results from an interaction with resident lung cells intravascular macrophages in the lung; there was no evi-is intuitively appealing. The lung contains several cell types that dence for bacterial interaction with either neutrophils or could serve as transducers of the pulmonary hemodynamic reendothelial cells. In the liver, GBS was found exclusively sponse to GBS. For example, the lung contains a substantial in Kupffer cells. In isolated piglet lungs perfused at a population of marginated neutrophils, a phagocytic cell known constant flow rate with blood-free physiologic salt solution, to elaborate various mediators incriminated in the response to GBS (lo6 to 10' organisms/mL) provoked concentration-GBS (I), including thromboxane AZ, sulfidopeptide leukotrienes, dependent increases in pulmonary vascular resistance. and toxic oxygen radicals (2-4). Pulmonary vascular endothelial Transmission electron microscopic examination of isolated cells also exhibit phagocytic activity ( 5 , 6) and produce eicosalungs indicated that GBS was localized within pulmonary noids with chemoattractant activity for neutrophils (7)....

Intrinsic Microbicidal Activity and Pulmonary Hypertension in Isolated Newborn Piglet Lungs

“…We and others have proposed that bacteriaor particulate-induced activation of an oxygen radical-dependent microbicidal mechanism residing within PIM is a key stimulus for mediator release and acute pulmonary hypertension (7). In support of this contention, we have shown that a substantial proportion of GBS deposits in the lungs of intact infant piglets, where approximately half of the organisms are nonviable within a 60-min period (7,8). Interestingly, the severity of the pulmonary hypertensive response was inversely related to the percentage of bacteria remaining alive in the lung.…”

“…At equivalent Pdo, GBS evoked greater increases in lung weight than U44069. DISCUSSION GBS deposits in the lungs of intact, newborn piglets, where the bacteria are apparently killed in part by an oxygen radicaldependent mechanism (7,8). In this complicated preparation, it is not possible to determine whether lung cells mount a pathophysiologically relevant microbicidal response to intravascular bacteria or whether cell populations remote from the lungs and/ or circulating blood cells kill bacteria that then localize in the lung.…”

“…The lung cells responsible for this bactericidal activity are unknown. Our previous electron microscopic analysis (8) suggested that GBS was localized in PIM with no evidence for bacterial interactions with either neutrophils or endothelial cells. This observation is consistent with reports from other laboratories.…”

“…The hydroxyl radical scavenger, DMTU, attenuates bacterial killing, TX accumulation, and pulmonary hypertension (7,9). Electron microscopic analysis indicated that GBS were associated exclusively with PIM; evidence for interactions with other lung cells, including endothelial cells and leukocytes, during the acute phase of pulmonary hypertension was not found (8).…”

“…Although we have previously demonstrated that GBS do indeed promote hypertension in isolated piglet lungs (8), it is not known whether lung cells mount a pathophysiologically relevant microbicidal response to intravascular bacteria or whether cell LUNG BACTERICIDAL ACTIVITY A N D PULMONARY HYPERTENSION 3 3 populations remote from the lungs and/or circulating blood cells Laboratories (Oxnard, CA) blood gas analyzer and maintained kill bacteria which then localize in the lung and evoke mediator at 7.35 to 7.5, 35 to 45 mm Hg, and 120 to 150 mm Hg, release and attendant hemodynamic abnormalities. Against this respectively.…”