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Polymorphonuclear leukocyte depletion with cyclophosphamide does not inhibit ozone-induced increase in airway permeability of susceptible mice

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:5307371
; ;  [1]
  1. Johns Hopkins Medical Inst., Baltimore, MD (United States)
The role of infiltrating polymorphonuclear leukocytes (PMNs) in acute oxidant injury of the lung is not clear. To determine whether acute ozone (O{sub 3})-induced increase in permeability is due to migrating PMNs or direct effects of O{sub 3} on the lung, genetically susceptible C57BL/6J mice were treated with cyclophosphamide (CY) in order to deplete PMNs. Following drug or vehicle (control) treatment, mice were exposed for 3 h to 2 ppm O{sub 3} or filtered air, and inflammation was assessed by inflammatory cell counts and total protein content (a marker of airway permeability) in bronchoalveolar lavage (BAL) and nasal lavage (NL) fluid. In vehicle control mice, O{sub 3} exposure caused a small but significant decrease in NL PMNs, and a highly significant increase in BAL PMNs and protein. CY treatment reduced total circulating peripheral blood granulocytes by 80%. Compared to vehicle controls, CY treatment also produced a highly significant attenuation of O{sub 3}-induced PMN influx in NL and BAL returns. However, in contrast to the hypothesized attenuating effect of PMN depletion on O{sub 3}-induced increase in permeability, CY treatment did not significantly reduce total BAL protein content compared to vehicle controls. Results indicate that PMNs do not play a major role in acute O{sub 3}-induced increase in murine airway permeability and suggest that acute O{sub 3}-induced lung injury may be due largely to direct effects of O{sub 3}.
OSTI ID:
5307371
Report Number(s):
CONF-9104107--
Conference Information:
Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Journal Volume: 5:4
Country of Publication:
United States
Language:
English