Effects of leukotriene B4 in the human lung. Recruitment of neutrophils into the alveolar spaces without a change in protein permeability.

Abstract

Leukotriene B4 (LTB4) is a major product of human alveolar macrophages and has potent chemotactic activity for neutrophils (PMN) in vitro. To evaluate the effects of LTB4 in the normal human lung, we instilled LTB4 (5 X 10-7M, 10 ml) into a subsegment of the right middle lobe and 0.9% NaCI (10 ml) into a subsegment of the lingula using a fiberoptic bronchoscope in 12 healthy human volunteers. 4 h later, we performed bronchoalveolar lavage of the same subsegments. Compared with the NaCl instillation, LTB4 caused a large increase in lavage total cells (NaCI = 6.8±1.0 X 106 vs. LTB4 = 26.4±5.0 X 106, P < 0.01), most of which were PMN (NaCl = 12.2±4.6% vs. LTB4 = 55.7±6.0%, P < 0.001). In contrast, there was only a small increase in lavage total protein, and the lavage total protein correlated weakly with lavage total cells and PMN. The production of superoxide anion by the lavage PMN in response to phorbol myristate acetate was similar to that of peripheral blood PMN. The migration of lavage PMN was normal toward the chemotactic peptide FMLP, but reduced toward LTB4 and zymosan-activated human serum. Morphometric analysis using transmission electron microscopy indicated a selective loss of small granules in the lung neutrophils as compared with peripheral blood neutrophils. The data indicate that in the normal human lung, LTB4 can recruit active PMN into the airspaces without causing a significant change in the protein permeability of the epithelial barrier.

Leukotriene B4 Triggers the In Vitro and In Vivo Release of Potent Antimicrobial Agents

“…LTB 4 administration to humans has been documented (29,65,66), with pharmacodynamic effects (␣-defensin and MIP-1␤ release (29) and PMN count variations (our unpublished data)) similar to what is reported in this study in monkeys without significant adverse events. Interestingly, low local levels of LTB 4 were reported in the lungs and brains of HIV-1-infected individuals afflicted with bacterial pneumonia and fungal encephalitis, respectively (67,68).…”

Hypoxic–ischemic brain damage induces distant inflammatory lung injury in newborn piglets

“…Total protein concentration in BALF is a direct indicator of vascular permeability and alveolar epithelium integrity (10). Increased vascular permeability can be a consequence of vascular damage or the result of a cell-mediated inflammatory response (21). In agreement, we found an increased concentration of IL-1β in lung tissue from HI piglets.…”

Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury

“…In the same sense, there were no differences in lung edema or protein content in the BAL fluid between genotypes, suggesting that MMP-9 modulates cell migration but not lung edema. It has been observed previously that cell infiltration and edema have different regulatory mechanisms during lung injury (31,51).…”